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Inhibition of the interaction of G protein G(o) with calcium channels by the calcium channel beta‐subunit in rat neurones.
Author(s) -
Campbell V,
Berrow N S,
Fitzgerald E M,
Brickley K,
Dolphin A C
Publication year - 1995
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1995.sp020735
Subject(s) - calcium channel , n type calcium channel , protein subunit , calcium , beta (programming language) , chemistry , biophysics , voltage dependent calcium channel , channel (broadcasting) , t type calcium channel , r type calcium channel , neuroscience , endocrinology , medicine , biochemistry , biology , computer science , gene , organic chemistry , programming language , computer network
1. The beta‐subunit has marked effects on the biophysical and pharmacological properties of voltage‐dependent calcium channels. In the present study we examined the ability of the GABAB agonist (‐) ‐baclofen to inhibit calcium channel currents in cultured rat dorsal root ganglion neurones following depletion of beta‐subunit immunoreactivity, 108‐116 h after microinjection of a beta‐subunit antisense oligonucleotide. 2.We observed that, although the calcium channel current was markedly reduced in amplitude following beta‐subunit depletion, the residual current (comprising both N‐ and L‐type calcium channel currents) showed an enhanced response to application of (‐) ‐baclofen. Therefore, it is possible that there is normally competition between activated G protein G(o) and the calcium channel beta‐subunit for binding to the calcium channel alpha 1‐subunit; and this competition shifts in favour of the binding of activated G(o) following depletion of the beta‐subunit, resulting in increased inhibition. 3. This hypothesis is supported by evidence that an antibody against the calcium channel beta‐subunit completely abolishes stimulation of the GTPase activity of G(o) by the dihydropyridine agonist S‐(‐) ‐Bay K 8644 in brain membranes. This stimulation of GTPase is thought to result from an interaction of G(o) alpha‐subunit (G alpha o) with its calcium channel effector which may operate as a GTPase‐activating protein. 4. These data suggest that the calcium channel beta‐subunit when complexed with the beta 1‐subunit normally inhibits its association with activated G(o). It may function as a GTPase‐activating protein to reduce the ability of activated G(o) to associate with the calcium channel, and thus limit the efficacy of agonists such as (‐) ‐baclofen.