Calcium channel beta subunit promotes voltage-dependent modulation of alpha 1 B by G beta gamma.
Voltage-dependent calcium channels (VDCCs) are heteromultimers composed of a pore-forming alpha1 subunit and auxiliary subunits, including the intracellular beta subunit, which has a strong influence on the channel properties. Voltage-dependent inhibitory modulation of neuronal VDCCs occurs primarily by activation of G-proteins and elevation of the free G beta gamma dimer concentration. Here we have examined the interaction between the regulation of N-type (alpha 1 B) channels by their beta subunits and by G beta gamma dimers, heterologously expressed in COS-7 cells. In contrast to previous studies suggesting antagonism of G protein inhibition by the VDCC beta subunit, we found a significantly larger G beta gamma-dependent inhibition of alpha 1 B channel activation when the VDCC alpha 1 B and beta subunits were coexpressed. In the absence of coexpressed VDCC beta subunit, the G beta gamma dimers, either expressed tonically or elevated via receptor activation, did not produce the expected features of voltage-dependent G protein modulation of N-type channels, including slowed activation and prepulse facilitation, while VDCC beta subunit coexpression restored all of the hallmarks of G beta gamma modulation. These results suggest that the VDCC beta subunit must be present for G beta gamma to induce voltage-dependent modulation of N-type calcium channels.
Meir
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Department of Pharmacology, University College London, London WC1E 6BT, United Kingdom. a.meir@ucl.ac.uk
Bell
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Stephens
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Dolphin
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D000818:Animals; D019556:COS Cells; D020864:Calcium Channels, N-Type / Q000737:chemistry* / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology; D019281:Dimerization; D019204:GTP-Binding Proteins / Q000502:physiology*; D007700:Kinetics; D046911:Macromolecular Substances; D008564:Membrane Potentials; D018408:Patch-Clamp Techniques; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection
D020864:Calcium Channels, N-Type; D046911:Macromolecular Substances; D011994:Recombinant Proteins; D019204:GTP-Binding Proteins