Heterotrimeric G proteins can directly gate ion channels without requiring cytoplasmic second messengers, demonstrating that a single G protein can have multiple distinct effectors.
Guanine nucleotide binding (G) proteins couple a variety of receptors to ionic channels. Until recently the pathway was thought to be indirect via cytoplasmic second messengers; now the heterotrimeric G proteins are known to act directly on K+ and Ca2+ channels. Here we summarize recent developments concerning this widespread mechanism which we call G protein gating of ion channels. A specific pertussis toxin-sensitive G protein called Gk, purified from human red blood cells, activates a unique K+ channel and Gk, or a similar G protein, couples this channel to muscarinic atrial receptors. The alpha-subunit (alpha k) at less than 10 pM mediates the effects, and alpha k also activates K+ channels directly in neurosecretory cells. The G protein stimulatory to adenylyl cyclase, Gs, gates directly through its alpha-subunit, specific Ca2+ channels in heart and skeletal muscle T tubules. Hence, one G protein can have two distinct effectors.
Brown et al. (Tue,) studied this question.
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