Presentation is loading. Please wait.

Presentation is loading. Please wait.

Regulation of Calcium Channels by G Protein-Coupled Receptors enzymes excitation- contraction gene transcription membrane potential exocytosis.

Similar presentations


Presentation on theme: "Regulation of Calcium Channels by G Protein-Coupled Receptors enzymes excitation- contraction gene transcription membrane potential exocytosis."— Presentation transcript:

1 Regulation of Calcium Channels by G Protein-Coupled Receptors enzymes excitation- contraction gene transcription membrane potential exocytosis

2 Transmitters decrease the calcium component of sensory neurone action potentials Dunlap K, Fischbach GD. Neurotransmitters decrease the calcium component of sensory neurone action potentials. Nature. 1978 Dec;276(5690):837-839.

3 Calcium channels are multimeric proteins Strock J, Diverse-Pierluissi MA. Ca2+ channels as integrators of G protein- mediated signaling in neurons. Mol Pharmacol. 2004 Nov;66(5):1071-1076. Epub 2004 Jul 21.

4 Cav1.1La1S DHP Skeletal muscle Excitation-contraction, Gene regulation Cav1.2La1C DHP Heart, endo., neurons Excitation-contraction, Hormone secretion Cav1.3La1D DHP Endocrine cells and neurons Hormone secretion, Gene regulation Cav1.4La1F Retina Tonic transmitter release Cav2.1P/Qa1A  -Ag Neurons Exocytosis Cav2.2Na1B  -Con Neurons Exocytosis Cav2.3Ra1E SNX482 Neurons Exocytosis Name Previous Alpha 1 Blocker Localization Function Name Classification of high-voltage activated calcium channels Strock J, Diverse-Pierluissi MA. Ca2+ channels as integrators of G protein- mediated signaling in neurons. Mol Pharmacol. 2004 Nov;66(5):1071-1076. Epub 2004 Jul 21.

5 Active zones contain calcium channels and synaptic vesicles that interact with adaptor proteins

6 Multiple G protein-mediated pathways inhibit voltage- dependent calcium channels Strock J, Diverse-Pierluissi MA. Ca2+ channels as integrators of G protein- mediated signaling in neurons. Mol Pharmacol. 2004 Nov;66(5):1071-1076. Epub 2004 Jul 21.

7 Cytoplasmic domains of the alpha 1 subunit of the calcium channel

8 Proteins that interact with the cytoplasmic domains of the alpha 1 subunit of the calcium channel can interact with each other

9 Proteins that interact with the cytoplasmic domains of the alpha 1 subunit of the calcium channel Strock J, Diverse-Pierluissi MA. Ca2+ channels as integrators of G protein- mediated signaling in neurons. Mol Pharmacol. 2004 Nov;66(5):1071-1076. Epub 2004 Jul 21.

10

11 Interaction of G  with the calcium channel mediates transmitter-induced voltage-dependent inhibition of calcium current Jarvis SE, Zamponi GW. Interactions between presynaptic Ca2+ channels, cytoplasmic messengers and proteins of the synaptic vesicle release complex. Trends Pharmacol Sci. 2001 Oct;22(10):519-525.

12 Binding of G  to the calcium channel displaces the beta subunit of the calcium channel Zamponi GW, Snutch TP. Modulation of voltage-dependent calcium channels by G proteins. Curr Opin Neurobiol. 1998 Jun;8(3):351-356.

13 Interaction of G  with the calcium channel induces the “reluctant” state Zamponi GW, Snutch TP. Modulation of voltage-dependent calcium channels by G proteins. Curr Opin Neurobiol. 1998 Jun;8(3):351-356.

14 Cross-talk beween G  and protein kinase C in the modulation of calcium current Cooper CB, Arnot MI, Feng ZP, Jarvis SE, Hamid J, Zamponi GW. Cross-talk between G-protein and protein kinase C modulation of N-type calcium channels is dependent on the G-protein beta subunit isoform. J Biol Chem. 2000 Dec;275(52):40777-40781.

15 Cross-talk beween G  and protein kinase C in the modulation of calcium current is dependent on the type of G  Cooper CB, Arnot MI, Feng ZP, Jarvis SE, Hamid J, Zamponi GW. Cross-talk between G-protein and protein kinase C modulation of N-type calcium channels is dependent on the G-protein beta subunit isoform. J Biol Chem. 2000 Dec;275(52):40777-40781.

16 Dual regulation of voltage-gated calcium channels by PtdIns (4,5)P 2 Wu L, Bauer CS, Zhen XG, Xie C, Yang J. Nature. 2002 Oct;419(6910):947-952.

17 Stabilization of P/Q calcium current by PIP 2 Tail current can be used to measure functional channels PIP2 slowed down rundown after patch excision Mg-ATP slowed down rundown after patch excision Wu L, Bauer CS, Zhen XG, Xie C, Yang J. Dual regulation of voltage-gated calcium channels by PtdIns(4,5)P2. Nature. 2002 Oct;419(6910):947-952.

18 PtdIns (4,5)P2 induced voltage-dependent inhibition Wu L, Bauer CS, Zhen XG, Xie C, Yang J. Dual regulation of voltage-gated calcium channels by PtdIns(4,5)P2. Nature. 2002 Oct;419(6910):947-952.

19 Receptor-mediated PIP2 hydrolysis: LHRH in frog sympathetic neurons Inhibition is voltage-independent Inhibition of PLC of U732122 Wu L, Bauer CS, Zhen XG, Xie C, Yang J. Dual regulation of voltage-gated calcium channels by PtdIns(4,5)P2. Nature. 2002 Oct;419(6910):947-952.

20 Multiple G protein coupled receptors mediate the inhibition of neuronal calcium channels Strock J, Diverse-Pierluissi MA. Ca2+ channels as integrators of G protein- mediated signaling in neurons. Mol Pharmacol. 2004 Nov;66(5):1071-1076. Epub 2004 Jul 21.

21 “willing” “reluctant” Binding of SNARE proteins to neuronal calcium channels

22 Muth JN, Varadi G, Schwartz A. Use of transgenic mice to study voltage-dependent Ca2+ channels. Trends Pharmacol Sci. 2001 Oct;22(10):526-532.

23

24 Diverse-Pierluissi M, Remmers AE, Neubig RR, Dunlap K. Novel form of crosstalk between G protein and tyrosine kinase pathways. Proc Natl Acad Sci U S A. 1997 May 13;94(10):5417-21. Time course of GABA-B receptor-mediated inhibition of N type current

25

26 PI3K promotes voltage dependent calcium channel trafficking in the plasma membrane Viard P, Butcher AJ, Halet G, Davies A, Nurnberg B, Heblich F, Dolphin AC. Nat Neurosci. 2004 Sep;7(9):939-946.

27 Effect of PI3K  -induced production of PIP3 on Ca v 1.2  /  2a currents Viard P, Butcher AJ, Halet G, Davies A, Nurnberg B, Heblich F, Dolphin AC. PI3K promotes voltage-dependent calcium channel trafficking to the plasma membrane. Nat Neurosci. 2004 Sep;7(9):939-946.

28 Effect of PI3K on Calcium Channel Membrane Localization Viard P, Butcher AJ, Halet G, Davies A, Nurnberg B, Heblich F, Dolphin AC. PI3K promotes voltage-dependent calcium channel trafficking to the plasma membrane. Nat Neurosci. 2004 Sep;7(9):939-946.

29 Effect of S574A mutation on the PI3K and myr-Akt/PKB-induced regulation of Ca v2.2 channels Viard P, Butcher AJ, Halet G, Davies A, Nurnberg B, Heblich F, Dolphin AC. PI3K promotes voltage-dependent calcium channel trafficking to the plasma membrane. Nat Neurosci. 2004 Sep;7(9):939-946.


Download ppt "Regulation of Calcium Channels by G Protein-Coupled Receptors enzymes excitation- contraction gene transcription membrane potential exocytosis."

Similar presentations


Ads by Google