1. NEUROPHYSIOLOGY, PHS 203
Prepared by OWOOLA
AKEEM G.
ABUAD

2. At the end of this course, students should be able to understand:
The nervous system (introduction)
Membrane potentials
Nerve impulse & its physiological properties
Synaptic transmission
Mechanism of force production
Functional adaptation of muscles
Functional organization of CNS
Autonomic neurotransmitter & autonomic effects

3. Introduction
2 systems are primarily responsible for body coordination & information processing: They are:
The endocrine system
The nervous system (NS)
The NS with its basic functions is the focus of this course. NS is basically divided into 2:
The peripheral nervous system: consists of afferent & efferent. The efferent is of involuntary (ANS: sympathetic, parasympathetic, & enteric NS) & voluntary (SNS) forms.
The central nervous system (CNS): consists of the brain & spinal cord.

4. NEURON (NERVE CELL)
Is the structural & fxnal unit of the NS. The human CNS contains abt 100 billion neurons. It also contains times this no of glial cells.
It is a complex organ; 40% of the human genes participate in its formation.
It evolved from primitive neuroeffector cells dt respond to various stimuli by contracting.
In complex animal, integration & transmission of nerve impulses are the specialized fxns of neurons. Whereas contraction is the specialized fxn of muscle cells.

5. It is classified based on d no of poles, fxn, & length of its axon.
Unipolar neurons: have one process (axon), wt difft segments serving as receptive surfaces & releasing terminals.
Bipolar neurons: have 2 processes: a dendrite dt carries information to d cell & an axon dt transmit information from d cell.
Pseudounipolar neurons: as d cell develops, a single process splits into 2, both of which fxn as axon- one going to d skin or mzl & another to the spinal cord

6. Multipolar neurons: have one axon & many dendrites
Multipolar neurons: have one axon & many dendrites. These are majorly find in motor neurons of spinal cord, pyramidal cell of hippocampus, & purkinje cell of cerebellum.
Based on function
Sensory (afferent) neurons: transmit impulses from receptor organs(for pain, vision, hearing etc.) to d CNS.
Motor (efferent) neurons: transmit impulse from the CNS to mzls & glands (effector organs).
Interneurons: transmit information from one neuron to another. They connect sensory neurons to motor neurons.

7. Based on the length of axon
Golgi type I neurons: have long axons. Their cell body is in d CNS, & their axons reach d peripheral organs.
Golgi type II neurons: have short axons & are present in cerebral cortex & spinal cord.
A typical neuron

8. Parts of Neurons
Nerve cell body (soma): contains d nucleus, neurofibrils, ribosome, mitochondria & golgi apparatus.
Dendrites: Extends outwards from d cell body & arborize extensively.
Axon (nerve fibre): originates from a thickened area of d cell body, the axon hillock. The 1st portion of d axon is called initial segment. It divides into terminal branches, each ending in a no of synaptic knobs-they contain granules (vesicles) which store synaptic transmitters secreted by nerves.

9. Varicosity: is a series of bulging areas along d axons where some neurons release their transmitters.
Some terminologies
Neurilemma: is d thin membrane dt forms d outermost of d nerve fibres.
Schwann cell: is a glial-like cells found along d axon. It is present in d neurilemma.
Myelin: is a protein-lipid complex wrapped around d axon. It I formed when a schwann cell wraps its membrane around an axon.
Nodes of Ranvier: is d uninsulated area where the myelin absent.

10. Unmyelinated axon: are simply surrounded by schwann cells without d wrapping of schwann cell membrane around axon.
Oligodendrogliocytes: are cells dt form d myelin in d CNS of mammals. In multiple scerosis, a crippling autoimmune dx, there is patchy destruction of myelin in d CNS.
Axoplasm: is d viscid ICF in d axon.
Protein & axoplasm transport
Nerve cells are secretory cells, but they are differ from other secretory cells in dt d secretory zone is generally at end of axon.

11. There are few if any ribosomes in axons & nerve terminals
There are few if any ribosomes in axons & nerve terminals. All necessary proteins are synthesized in ER & GA of cell body & then transported along d axon to d synaptic knobs.
Axoplasmic flow: is d process by which all d synthesized proteins are transported along d axon to d synaptic knobs.
Wallerian degeneration: is d degenerative change in d distal cut end of d nerve fibre.
Nerve fibre: is an axon. It is classified based on:

12. Structure: i. myelinated & ii. nonmyelinated nerve fibres.
Distribution: i. somatic (supply skeletal mzls) & ii. autonomic (supply difft internal organs) nerve fibres.
Origin: i. cranial (arise from d brain) & ii. spinal (arise from spinal cord) nerve fibres.
Function: i. sensory & ii. motor nerve fibres.
Secretion of neurotransmitter: i. adrenergic (secrets NA) & cholinergic (secrets Acetylcholine) nerve fibres.

13. Diameter & Conduction of impulse:
type A∝- for proprioception (12-20mm; m/s)
type A𝛽− for touch, pressure, & motor (5-12mm; m/s)
type A𝛾− motor to mzl spindles (3-6mm; 15-30m/s
type A𝛿−for pain, cold, & touch (2-5mm; 12-30m/s)
type B- for preganglionic autonomic (<3mm; 3-15m/s)
type C- for pain, temp., mechanoreception, reflex responses ( mm; 0.5m/s).

14. Note dt depending on origin,
type A∝ could either be type Ia or Ib.
type A𝛽 is also called type II
type A𝛿 is also called type III
A & B fibres are myelinated but C fibres are not.
Generally, d greater d diameter of a nerve fibre, d greater its speed of conduction.
Large axons are concerned I0ly wt proprioceptive sensation, somatic motor fxn, conscious touch, & pressure, where smaller axons subserve temp. & pain sensations, & autonomic fxn.

15. Membrane potentials (MP)
Are charge difference between the ICF & ECF in all cells, due to the differential distribution of ions.
It affects the activity of excitable cells & the trans membrane movement of all charged substance.

16. Resting membrane potential (RMP)
Is the potential difference between inside & outside of the cell across the cell membrane under resting conditions.
The inside of the cell is -vely charged with respect to the outside, +vely charged.
The polarity (+ve or –ve) of the MP is stated in terms of the sign of the excess charge on the inside of the cell. E.g. if the ICF has an excess –ve charge & potential difference across the membrane has a magnitude of 70 mV, the MP is -70 mV.

17. The magnitude of RMP generally ranges from -40 to -75 mV.
RMP is generated by the diffusion of ions and are determined by ionic concentration differences across the membrane & the membrane’s relative permeability to ions.
Transient changes in the MP from its resting level produce electric signals that can alter cell activities. Such ways are the most important ways that nerve cells process & transmit information.
Forms of the electric signal: (a) graded potential & (b) action potential

18. Graded potential
Are changes in the MP that are confined to a relatively small region of plasma membrane & die out within 1 to 2mm of their site of region.
The magnitude of their potential change is variable (graded) & is related to the magnitude of the stimulus e.g. receptor potentials, synaptic potentials, end-plate potentials, etc. They are important in signaling over short distances.

19. NOTE:
Adjectives such as membrane, resting, action, and graded define conditions under which the potential is measured or the way it develops.
The terms depolarize, hyperpolarize, and repolarize describe the direction of changes in the MP relative to the resting potential.
The membrane is said to be depolarized when its potential is less –ve (closer to zero) than the resting level. The membrane is hyperpolarized when the potential is more –ve than the resting level.
When a MP that has been either depolarized or hyperpolarized returns towards the resting level, it is said to be repolarizing.
Overshoot refers to a reversal of the MP polarity, i.e. when the inside of a cell becomes +ve.

20. Action potential (AP)
Are rapid alterations in the MP when stimulated.
It may last only 1 min, during which time the MP may change from -70 mV to +30 mV, & then repolarize to its RMP.
Nerve & muscle cells as well as some endocrine, immune, & reproductive cells have plasma membranes capable of producing AP. These membrane are called excitable membranes, & their ability to generate AP is known as EXCITABILITY.
The propagation of AP is the mechanism used by NS to communicate over long distances.

21. Stimulus artifact: is a brief irregular deflection of the baseline when the stimulus is applied.
Latent period: is the time it takes the impulse to travel along the axon from the site of stimulation to recording electrodes. It is proportional to the distance between the stimulating & recording electrode.
The successive stages of the Action Potential
Resting stage
Depolarization stage
Repolarization stage

22. Resting stage: is the RMP before the P begins
Resting stage: is the RMP before the P begins. The membrane is said to be polarized during this stage bcos of the -70 mV –ve MP that is present.
Depolarization stage: At this stage, the membrane suddenly becomes permeable to sodium ions, allowing tremendous numbers of +vely charged sodiums to diffuse to the interior of the axon.
The normal polarized state of -70 mV is immediately neutralized by the inflowing +vely charged sodium ions, with the potential rising rapidly in the +ve direction.
In large nerve fibres, the great excess of +ve sodium ions moving to the inside causes the MP to overshoot beyond the zero level & to become somewhat +ve.

23. Repolarization stage: Within a few 10, 000ths of a second after the membrane becomes highly permeable to sodium ions, the sodium channels begin to close & the potassium channels open more than normal. Then, rapid diffusion of potassium ions to the exterior re-establishes the normal –ve RMP.

24. Roles of other ions during the AP
Imperment –vely charged ions (anions) inside axon
Protein molecules, many organic compounds, sulphate compounds etc. are –vely charged ions present inside the axon. Bcos they cannot leave the ICF of the axon, any deficit of +ve ions inside the membrane leaves an excess of these imperment –ve anions.
There4, these imperment –ve ions are responsible for the –ve charge inside the fibre when there is a net deficit of +vely charged K ions & other +ve ions.

25. Calcium ions (Ca2+):
In some cells, calcium serves along with (or instead of) sodium to cause most of the AP. Like sodium pump, the calcium pump pumps calcium ion from the ICF to the ECF (or into the ER of the cell), creating a Ca2+ gradient of about fold.
This leaves an ICF concn of Ca2+ of about molar, in contrast to ECF concn of about molar.

26. In addition, there are voltage-gated Ca2+- channels
In addition, there are voltage-gated Ca2+- channels. These channels are slightly permeable to Na+ as well as Ca2+; when they open, both Ca2+ & Na+ flow to the ICF of the fibre.
There4, these channels are also called Ca2+_ Na+ channels but are slow to become activated in contrast to the Na+_ channel which are called fast channels.
Ca2+-channels are numerous both in cardiac & smooth muscle. In fact, AP are caused almost entirely by activation of slow Ca2+-channels in some types of smooth muscle. The fast Na+- channel are hardly present.

27. Increased Permeability of the Na+-channels when there is deficit Ca2+
The concn of Ca2+ in the ECF also has an effect on voltage level at which the Na+-channels become activated. When there is deficit of Ca2+, the Na+- channels become activated (opened) by very little increase of MP from its normal –ve level.
There4, the nerve fibre becomes highly excitable, sometimes discharging repetitively without provocation rather than remaining in the resting state.

28. Initiation of the AP
A +ve feedback vicious cycle opens the Na+- channels
First, as long as the membrane of the nerve fibre remains undisturbed, no AP occurs in the normal nerve. However, if any events causes enough initial rise in the MP from -70 mV towards ZERO level, the rising voltage itself causes many voltage-gated Na+-channels to begin opening.
This allows rapid inflow of Na+, which causes a further rise in the MP, thus opening still more voltage-gated Na+-channels & allowing more streaming of Na+ to the ICF of the fibre.

29. This process is a positive-feedback vicious cycle that, once the feedback is strong enough, continues until all the voltage-gated Na+- channels have become activated, opened (depolarization). This is followed by overshoot.
Then, within another fraction of milliseconds, the rising MP causes closure of the Na+-channels as well as opening of K+-channels, & the AP soon terminates (repolarization).
An AP will not occur until the initial rise in MP is great enough to create the vicious cycle describe above. This occurs when the no of Na+ entering the fibre becomes greater than the no of K+ leaving the fibre.

30. A sudden rise in MP of 15 mV is usually required.
There4, a sudden increase in MP in a large nerve fibres from -70 mV up to -55 mV usually causes the explosive development of an AP.
This level of -55 mV is said to be threshold for stimulation.
AP obeys all or none law which states that once an AP has been elicited at any point on the membrane of normal fibre, the depolarization process travels over the entire membrane if the conditions are right, or it does not travel at all if conditions are wrong.

31. A new AP cannot occur in an excitable fibre as long as the membrane is still depolarizing from the preceding AP. The reason is that shortly after the AP is initiated, the Na+-channels (or Ca+- channels or both) become inactivated, & no amount of excitatory signal applied to these channels at this point will open the inactivation gates.
The only condition that will allow them to reopen is for the MP to return to or near the original RMP level. Then, within another small fraction of a second, the inactivation gates of the channels open, & a new AP can be initiated.

32. Refractory Period: is the period at which the nerve does not elicit AP.
Absolute refractory period (ARP): is the period during which a 2nd AP cannot be elicited, even with a strong stimulus. It is 1/2500 secs in large myelinated nerve fibres.
Relative refractory period (RRP): is the period when an AP can be elicited from the nerve incase the strength of stimulus is maximum. It begins when the ARP ends. The AP elicited has a lower depolarization velocity & a lower overshoot potential than does the normal AP.

33. Plateau
Occurs when the excited membrane does not repolarize immediately after depolarization. Instead, the potential remains a plateau near the peak of the spike potential for many ms & only then repolarization begins.
It prolongs the period of depolarization, occurs in heart muscle fibres where it lasts for about 0.2 to 0.3 sec & causes contraction of heart muscle to last for this same long period.
Causes: (i) opening of fast voltage Na+-channels causes the spike portion of the AP whereas the slow, prolonged opening of the slow Ca2+- Na+channels mainly allows Ca2+ to enter the fibre.

34. This is largely responsible for the plateau portion of the AP
This is largely responsible for the plateau portion of the AP. (ii) the voltage-gated K+-channels are slower than usual to open, often not opening very much until the end of plateau.
Saltatory Conduction: is the conduction of AP from node to node. It should be noted that AP occurs the nodes bcos ions flow with ease through the node of Ranvier. That is, electrical current flows through the surrounding ECF outside the myelin sheath as well as through the axoplasm inside the axon from node to node, exciting successive nodes one after another. Thus, the nerve impulse jumps down the fibre.

35. Inhibition of Excitability
A high ECF Ca2+ concn decreases membrane permeability to Na+ & simultaneously reduces excitability. There4, Ca2+ are said to be ‘stabilizer’.
Local Anesthetics: other important stabilizers are many substances used clinically as local anesthetics e.g. Procain, lidocaine, & tetracaine. Most of these act directly on the activation gates of the Na+-channels, making it much more difficult for these gates to open, thereby reducing membrane excitability. When excitability has been reduced so low that the ratio of AP strength to excitability threshold is reduced below 1.0, nerve impulse fail to pass.

36. Excitability curve or strength-duration curve
This is the curve that demonstrates the relationship between the strength & duration of a stimulus. The stimulus is plotted (in volts) on the y-axis while the duration is plotted on the x-axis.
Features of the curve
Rheobase: Is the minimum strength of stimulus which can excite the tissue.
Utilization time: Is the minimum time required for a rheobasic strength to excite the tissue.
Chronaxie: Is the minimum which a stimulus with double the rheobasic strength can excite the tissue.

37. The measurement of chronaxie determines the excitability of tissue: the longer the chronaxie, the less excitable is the tissue.
Chronaxie is 10 times more in skeletal muscles of infants than in skeletal muscles of adults. It is prolonged in muscles paralyzed due to nervous disorders, and in progressive neural diseases, it is prolonged gradually. It is shortened by increased temperature & prolonged in cold temperature.

38. GLIAL CELLS (NEUROGLIA)
They do not conduct nerve electrical signals.
They protect and nourish the neurons.
They determine the growth, nourishment and effective synapses of neurons.
They maintain the composition of the fluid surrounding the neurons in the nervous system. They also actively enhance synaptic function

39. Types of glial cells in the CNS
Astrocytes
are the most abundant glial cells.
serve as scaffolding to guide neurons to their proper destination during brain development in the fetus.
establish blood brain barrier (BBB).
play a role in the uptake and termination (of the activities) of neurotransmitters.
enhance the formation and functions of synapses-they communicate with each other and with neurons.

40. Oligodendrocytes
form myelin around the axons of the CNS.
Microglia
acts as the immune defence cells of the CNS. They are similar tissues like monocytes.
Ependymal cells
line the cavities of the brain.
contribute to the formation of CSF.
have cilia whose beating helps the CSF to flow throughout the brain cavities.
also act as stem cells in the brain & have potential to form other glial cells or new neurons in certain part of the brain. Neurons is most part of the brain are irreplaceable.

41. Types glial cells in the PNS
Schwann cells
are wound around the nerve fibres in the PNS.
produce myelin sheaths.
are similar to the oligodendrocytes in the CNS.
also promote regeneration of damaged fibres.
Satellite cells
surround the cell bodies of neurons in the ganglia of the PNS

42. A typical glia cell

43. SYNAPSE Is the place where one neuron connects to another.
Includes presynaptic neuron, the postsynaptic neuron with receptors, & the space between them.
The electrical signal in the axon of the first neuron triggers a chemical signal to be released into the gap that is tasted by receptors in the second neuron.
Types of synapse:
Synapse are basically of 2 types: chemical synapse and electrical synapse.

44. Chemical synapse
electrical activity in the presynaptic neuron is converted (through the activation of voltage- gated Ca2+ channels) into the release of a neurotransmitter.
The neurotransmitter binds to receptors which are located in the plasma membrane of the postsynaptic neurons.
This forms a neurotransmitter-receptor complex which may initiate an electrical response or a secondary messenger pathway that may either excite or inhibit the postsynaptic neuron.

45. Chemical synapse & stages of signal transmission at a chemical synapse

46. Excitatory synapses
the postsynaptic neuron becomes more excitable as a result of synaptic events.
excitatory neurotransmitter (Ach, most common) binds to its receptor on the postsynaptic neuron.
This leads to a few K+ moving out of the cell, & many Na+ moving into d cell. Both K+ & Na+ carry one +ve charge.
So, d inside of the cell membrane becomes slightly more +ve & mild depolarization called an excitatory postsynaptic potential (EPSP) occurs.
EPSP confines only to d synapse. It is graded potential. However, if EPSP is strong enough, it causes d opening of voltage-gated Na+_ channels in d initial segment of axon, leading to AP dvpt.

47. Inhibitory synapses
the postsynaptic neuron becomes less excitable as a result of synaptic events.
inhibitory neurotransmitter [GABA (most common), dopamine, & glycine] binds to its receptor on the postsynaptic neuron.
This leads to K+ leaving the cell, & Cl- entering the cell.
the inside of the cell membrane becomes slightly more –ve compared to d RMP .
This leads to hyperpolarization called inhibitory postsynaptic potential (IPSP).
IPSP inhibits synaptic transmission.

48. Chemical synapses can be classified according to the neurotransmitter released: Glutamatergic (often excitatory), GABAergic (often inhibitory), & cholinergic etc.
It can have effects on the postsynaptic cell because of the receptor signal transduction.
Impulse transmission is slow due to synaptic delay.
It is active (require ligand-gated channels).

49. Electrical synapse
the presynaptic & postsynaptic cell membranes are connected together by gap junctions which allow impulse to pass through them & thus cause voltage changes in d presynaptic cell to induce voltage changes in d postsynaptic cell.
The transmission of impulse is very rapid (no synaptic delay), bidirectional (post-synaptic cell can send messages to the presynaptic cell) , & it may not produce a large depolarization to initiate an impulse in the post-synaptic cell.

50. illustration of an electrical synapse with gap junctions

51. Synapses can be classified based on the type of cellular structure of postsynaptic target, onto which d axon terminal projects (connects). The axon can synapse into :
the bloodstream (Axo-secretory)
another axon or axon terminal (Axo-axonic)
a dendrite (Axo-dendritic)
a cell body (Axo-somatic)
extracellular fluid (Axo-extracellular) or diffusely into the adjacent nervous tissue

52. classes of synapse based on the cellular structure of the post-synaptic target

53. Role of synapse in memory formation
When neurotransmitters activate receptors across d synaptic cleft, d connection between d two neurons is strengthened if both neurons are active at d same time (due to d mechanism of receptor signaling).
The strength of two connected neural pathways is thought to result in d storage of information which results in memory. This process of synaptic strengthening is known as long-term potentiation, LTP.

54. Plasticity of synapses can be controlled in d presynaptic cell by altering d release of neurotransmitters.
The postsynaptic cell can be regulated by altering d function & number of its receptors.
Changes in postsynaptic signaling are commonly associated with N-methyl-d-aspartic acid receptor (NMDAR)-dependent LTP & long- term depression (LTD), which are d most analyzed forms of plasticity at excitatory synapses.

55. Mzl cells
Like neurons can be excited to produce AP.
Unlike neurons, they av a contractile mechanism dt is activated by AP.
The contractile proteins are abundant in mzl, where they bring abt mzl contraction.
Types: (a) skeletal (b) cardiac, & (c) smooth mzls
Skeletal mzls
Makes up d great mass of somatic musculature.
Has well-developed cross-striations.
It does not normally contract in d absence of nervous stimulation. It is voluntarily control.

56. Cardiac mzls
Is also cross-striated, but fxnally syncytial & contracts rhythmically in d absence of external innervation owing to d presence of pacemaker cells dt discharge spontaneously.
Smooth mzls
Lack cross-striations.
In most hollow visceral, it is fxnally syncytial & contains pacemakers dt discharge irregularly.
Found in d eye & in some other location dt is not spontaneously active.

57. Organization of skeletal mzl
Skeletal mzl is made up of individual mzl fibres dt are d ‘building blocks’ of muscular system in d same way dt d neurons are d building block of d NS.
Arrangement
Most skeletal mzls begin & end in tendons & d mzl fibres are arrange parallel between d tendinous ends, so dt d force of attraction of d unit is additive.
The mzl fibres: Each mzl fibre is a single cell, multinucleated, long, cylindrical, & surrounded by a cell membrane called sarcolemma.

58. Composition of d mzl fibres
The mzl fibres are made up myofibrils, which are divisible into individual filaments (thin & thick composed of d contractile proteins).
The thin filament
Are I0ly made of d protein actin. They are found in all other cells of d body but in a less-organized fashion.
Other proteins found in d thin filaments are tropomyosin & troponin.

59. The thin filaments form d light I bands
The thin filaments form d light I bands. Dark Z lines transect d fibrils & connect to d thin filaments.
The area between two adjacent Z lines is called a SARCOMERE.
Sarcomere is fxnal unit of skeletal mzl. i.e, d smallest component of a mzl fibre dt is capable of contraction.

60. The thick filaments
Form d dark A bands. There is lighter H (region where, when d mzl is relaxed, d thin filaments do not overlap d thick filaments) band in d centre of dark A.
A transverse M line (site of reversal of polarity of d myosin molecules in each of d thick filaments) is seen in d middle of d H band.
Are made up of d proteins myosin-II which contain heavy chains & light chains.

61. The myosin have 2 globular heads (made up of d light chains & d amino terminal portions of d heavy chains) & a long tail.
One head contains an actin-binding site & d 2nd head is a catalytic site dt hydrolysis ATP into ADP & Pi.
In skeletal mzl, mg+ must be attached to ATP on d myosin cross bridge b/4 myosin ATPase can split d ATP- b/4 d cross bridge links wt actin molecule.
The heads & necks of d myosin molecules form cross-links to actin.

62. Levels of organization in a skeletal mzl.
Whole mzl (an organ)
Mzl fibre (a cell)
Myofibril (a specialized intracellular structure)
Thick & thin filament (cytoskeletal elements)
Myosin & actin (proteins)
Factors dt determine contractile mechanism in skeletal mzl:
The proteins myosin-II
Actin &
Troponin (troponin I, troponin T, troponin C).

63. Mechanism of force production
The term activation (or muscle activation) designates the set of events dt link the excitation with the contractile machinery and resulting in force production.
The process involves the following steps:
Ach released from d terminal of a motor neuron initiates an AP in d mzl cell dt-d AP is propagated over d entire surface of d mzl cell membrane.
The surface of electric activity is carried into d central portions of d mzl fibre by d T tubules.

64. Spread of d AP down d T tubules triggers d release of stored Ca2+ from d adjacent lateral sacs of d sarcoplasmic reticulum.
Released Ca2+ binds wt troponin & changes its shape so dt d troponin-tropomyosin complex is physically pulled aside, uncovering actin’s cross bridge binding sites.
Exposed actin sites bind wt myosin cross bridges , which have previously been energized by d splitting of ATP into ADP + Pi + energy by d myosin ATPase site on d cross bridges.

65. This causes d cross bridge to bend , producing a power stroke dt pulls d thin filament inward.
Inward sliding of all d thin filaments surrounding d thick filament shortens d sarcomere (causes mzl contraction).
ADP & Pi are released from d cross bridge during d power stroke.
Attachment of a new molecule of ATP permits detachment of d cross bridge, which returns to its original conformation.

66. Splitting of d fresh ATP molecule by myosin ATPase energizes d cross bridge once again.
If Ca2+ is still present so dt d troponin-tropomyosin complex remains pulled aside, d cross bridges go through another cycle of binding & bending, pulling d thin filament in even further.
When there is no longer AP & Ca2+ has been actively returned to its storage site in d sarcoplasmic reticulum’s lateral sacs, d troponin-tropomyosin complex slips back into d blocking position, actin & myosin no longer bind at d cross-bridges, & d thin filaments slide back to their resting position as relaxation takes place.

67. Role of Ca2+ in Relaxation
The contractile process is turned off when Ca2+ is returned to d lateral sacs upon cessation of local electrical activity.
The sarcoplasmic reticulum possesses an energy- consuming carrier, Ca2+-ATPase pump, which actively transports Ca2+ from d cytosol & concentrates it in d lateral sacs.
When acetyl cholinesterase removes Ach from d neuromuscular junction, d mzl fibre AP ceases.

68. When there is no longer a local AP in d T tubules to trigger d release of Ca2+, d ongoing activity of d sarcoplasmic reticulum’ Ca2+pump returns d released Ca2+ back into d lateral sacks.
Removal of cytosolic Ca2+ allows d troponin- tropomyosin complex to slip back into its blocking position, so dt actin & myosin are no longer able to bind at d cross bridges. The thin filaments, freed from cycles of cross-bridge attachment & pulling, are able to return to their resting position. Relaxation has occurred.