Presentation on theme: "Membrane potentials 膜电位 Xia Qiang, MD & PhD Department of Physiology Room C518, Block C, Research Building, ZJU School of Medicine Tel: 88208252 Email:"— Presentation transcript:
Membrane potentials 膜电位 Xia Qiang, MD & PhD Department of Physiology Room C518, Block C, Research Building, ZJU School of Medicine Tel: 88208252 Email: firstname.lastname@example.org
Resting membrane potential （静息电位） A potential difference across the membranes of inactive cells, with the inside of the cell negative relative to the outside of the cell Ranging from –10 to –100 mV
Depolarization occurs when ion movement reduces the charge imbalance. A cell is “polarized” because its interior is more negative than its exterior. Overshoot refers to the development of a charge reversal. Repolarization is movement back toward the resting potential. Hyperpolarization is the development of even more negative charge inside the cell. （极化） （去极化） （超极化） （复极化） （超射）
chemical driving force electrical driving force ++++++++++++++++ - - - - - - - - - - - - - - - - - electrochemical balance
The Nernst Equation: K + equilibrium potential (E K ) (37 o C) R=Gas constant T=Temperature Z=Valence F=Faraday’s constant （钾离子平衡电位） German physical chemist and physicist
Begin: K + in Compartment 2, Na + in Compartment 1; BUT only K + can move. Ion movement: K + crosses into Compartment 1; Na + stays in Compartment 1. buildup of positive charge in Compartment 1 produces an electrical potential that exactly offsets the K + chemical concentration gradient. At the potassium equilibrium potential:
Begin: K + in Compartment 2, Na + in Compartment 1; BUT only Na + can move. Ion movement: Na + crosses into Compartment 2; but K + stays in Compartment 2. buildup of positive charge in Compartment 2 produces an electrical potential that exactly offsets the Na + chemical concentration gradient. At the sodium equilibrium potential:
Mammalian skeletal muscle cell -95 mV-90 mV Frog skeletal muscle cell -105 mV-90 mV Squid giant axon -96 mV-70 mV E k O bserved RP Difference between E K and directly measured resting potential
Electrogenic Hyperpolarizing Role of Na + -K + pump: Establishment of resting membrane potential: Na+/K+ pump establishes concentration gradient generating a small negative potential; pump uses up to 40% of the ATP produced by that cell!
Click here to play the Sodium-potassium Pump Flash Animation
Origin of the normal resting membrane potential K + diffusion potential Na + diffusion Na + -K + pump
Action potential （动作电位） Some of the cells (excitable cells) are capable to rapidly reverse their resting membrane potential from negative resting values to slightly positive values. This transient and rapid change in membrane potential is called an action potential
The size of a graded potential (here, graded depolarizations) is proportionate to the intensity of the stimulus.
Graded potentials can be:EXCITATORYorINHIBITORY (action potential(action potential is more likely)is less likely) The size of a graded potential is proportional to the size of the stimulus. Graded potentials decay as they move over distance.
The rapid opening of voltage-gated Na + channels explains the rapid-depolarization phase at the beginning of the action potential. The slower opening of voltage-gated K + channels explains the repolarization and after hyperpolarization phases that complete the action potential.
An action potential is an “all-or-none” sequence of changes in membrane potential. Action potentials result from an all-or-none sequence of changes in ion permeability due to the operation of voltage-gated Na + and K + channels. The rapid opening of voltage-gated Na + channels allows rapid entry of Na +, moving membrane potential closer to the sodium equilibrium potential (+60 mv) The slower opening of voltage-gated K + channels allows K + exit, moving membrane potential closer to the potassium equilibrium potential (-90 mv)
Click here to play the Voltage Gated Channels and Action Potential Flash Animation
Mechanism of the initiation and termination of AP
Re-establishing Na + and K + gradients after AP Na + -K + pump “Recharging” process
Properties of action potential (AP) Depolarization must exceed threshold value to trigger AP AP is all-or-none AP propagates without decrement
Voltage Clamp How to study ? Nobel Prize in Physiology or Medicine 1963 "for their discoveries concerning the ionic mechanisms involved in excitation and inhibition in the peripheral and central portions of the nerve cell membrane" Eccles Hodgkin Huxley
Currents recorded under voltage clamp condition
Patch Clamp Nobel Prize in Physiology or Medicine 1991 "for their discoveries concerning the function of single ion channels in cells" Erwin Neher Bert Sakmann
Video The Squid and its Giant Nerve Fiber "The Squid and its Giant Nerve Fiber" was filmed in the 1970s at Plymouth Marine Laboratory in England. This is the laboratory where Hodgkin and Huxley conducted experiments on the squid giant axon in the 1940s. Their experiments unraveled the mechanism of the action potential, and led to a Nobel Prize. Long out of print, the film is an historically important record of the voltage-clamp technique as developed by Hodgkin and Huxley, as well as an interesting glimpse at how the experiments were done.
Factors affecting excitability Resting potential Threshold Channel state
The propagation of the action potential from the dendritic to the axon-terminal end is typically one-way because the absolute refractory period follows along in the “wake” of the moving action potential.
SUMMARY Resting potential: K + diffusion potential Na + diffusion Na + -K + pump Graded potential Not “all-or-none” Electrotonic propagation Spatial and temporal summation
Action potential Depolarization: Activation of voltage-gated Na+ channel Repolarization: Inactivation of Na+ channel, and activation of K+ channel Refractory period Absolute refractory period Relative refractory period
Case Primary Hyperkalemic Periodic Paralysis ( 原发性高血钾性周期性麻痹 ) A l0-year-old boy has sporadic attacks of muscle paralysis. The patient has four brothers, all of whom have suffered similar symptoms. The onset of these attacks is characterized by pain associated with contractures of the affected muscles. Later in the attack those muscles may become paralyzed and more flaccid. Episodes of pain and contracture frequently occur without subsequent paralysis. Analysis of blood samples taken during an attack indicates that the patient is hyperkalemic. Plasma K+ levels are normal when the patient is not having an attack. Biopsies of the patient's muscle show a significantly diminished level of intracellular K+ (83 mmol/kg wet tissue) compared with control muscle (95 mmol/kg wet tissue). Basal tissue activity of Na+, K+-ATPase is normal. Paralytic attacks are accompanied by diuresis with increased K+ excretion. Electrophysiologic studies of the patient show that during an attack the excitability and conduction times of motor neurons are normal, as is the function of the neuromuscular junction. Microelectrode studies show that during an attack the magnitude of the resting membrane potential of skeletal muscle cells is diminished compared with control muscle fibers. Electromyography shows that early pared with control muscle fibers. Electromyography shows that early in an attack the muscle contractures are associated with spontaneous action potentials in the affected muscle fibers. Later, during the paralytic phase of an attack, muscle cells become electrically inexcitable - the muscle cells do not respond electrically to stimulation of the motor axons that innervate them. A paralytic attack can be relieved by treating the patient with an insulin injection. Long-term administration of the 2-agonist salbutamol dramatically diminishes the occurrence of episodes of both contractures and subsequent paralytic attacks.
Questions l. What might account for the patient being hyperkalemic during an attack, while the potassium concentration in his skeletal muscle cells is diminished? What types of alterations of basic cellular processes might underlie this situation? 2. What explains the observation that the magnitude of the resting membrane potentials of the patient's skeletal muscle fibers is diminished during an attack? 3. Does the diminished resting membrane potential have anything to do with the spontaneous action potentials and contractures that occur early in an attack, before paralysis sets in? 4. How might the diminished resting membrane potential contribute to the paralytic phase of an attack, in which muscle cells are electrically inexcitable? 5. How might insulin terminate a paralytic attack? 6. How might long-term administration of salbotamol diminish the occurrence of attacks of contractures and paralysis?
Answers l. The hyperkalemia with a concomitant decrease in the amount of K+ in muscle cells suggests that the hrperkalemia is caused bf K+ efflux from the cells, but the cause of K+ efflux is not known. Net K+ efflux from muscle cells might occur because of diminished fate of K+ accumulation by the Na+, K+-ATPase, or an increased rate of K+ efflux from the cell, or a combination of both factors. The observation that Na+, K+-ATPase is normal does not completely rule out a malfunction of this protein during an attack. 2. Elevating extracellular K+ and decreasing the intracellular level of K+ would decrease the potassium equilibrium potential and thus decrease the magnitude of the resting membrane potential. 3. The decreased magnitude of the resting membrane potential initially brings the muscle cells closer to threshold for firing an action potential. For this reason, spontaneous, small fluctuations in the resting membrane potential may reach threshold. This results in spontaneous action potentials and contractions of skeletal muscle cells and leads to the contractures experienced by the patient early in an attack. 4. Prolonged depolarization of the muscle cell plasma membrane will lead to voltage inactivation of Na+ channels in the membrane, which will result in the muscle cell's being unable to fire an action potential. This is believed to be the cause of the paralytic phase of an attack and is supported by the observation that during the paralytic phase, the patient's skeletal muscle cells may be electrically inexcitable. 5. Insulin immediately and powerfully promotes the uptake of K+ by cells and the extrusion of Na+ from cells. Administration of insulin thus corrects the hyperkalemia restores cellular K+ levels toward normal, and causes the resting membrane potential for the affected skeletal muscle cells to become closer to the normal resting value. In this way insulin is believed to terminate an attack of contractures or paralysis in these patients. 6. Long-term administration of salbutamol, a β2-agonist, increases the activity of the Na+, K+-ATPase in skeletal muscle cells. In this way, salbutamol administraion leads to increased sequestration of K+ in muscle cells. Apparently this helps to prevent the K+ efflux that underlies episodes of hyperkalemia with resultant contractures that may be followed by periods of paralysis.