Calcium channel beta subunit promotes voltage-dependent modulation of alpha 1 B by G beta gamma - PubMed (original) (raw)

Calcium channel beta subunit promotes voltage-dependent modulation of alpha 1 B by G beta gamma

A Meir et al. Biophys J. 2000 Aug.

Abstract

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.

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References

1. 1. J Gen Physiol. 2000 Feb;115(2):175-92 - PubMed
2. 1. Eur J Neurosci. 1997 Jun;9(6):1252-61 - PubMed
3. 1. J Physiol. 2000 Jun 1;525 Pt 2:377-90 - PubMed
4. 1. Proc Natl Acad Sci U S A. 1986 Apr;83(7):2162-6 - PubMed
5. 1. J Physiol. 1991 Aug;439:181-214 - PubMed

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