ROLES OF G-PROTEINS IN COUPLING OF RECEPTORS TO IONIC CHANNELS AND OTHER EFFECTOR SYSTEMS

Guanine nucleotide binding (G) proteins are heterotrimers that couple a wide range of receptors to ionic channels. The coupling may be indirect, via cytoplasmic agents, or direct, as has been shown for two K+ channels and two Ca2+ channels. One example of direct G protein gating is the atrial muscarinic K+ channel K+ [ACh], an inwardly rectifying K1 channel with a slope conductance of 40 pS in symmetrical isotonic K+ solutions and a mean open lifetime of 1.4 ms at potentials between -40 and - 100 mV. Another is the clonal GH, muscarinic or somatostatin K+ channel, also inwardly rectifying but with a slope conductance of 55 pS. AG protein, G., purified from human red blood cells WC) activates K+[ACh] channels at subpicomolar concentrations; its a subunit is equi-potent. Except for being irreversible, their effects on gating precisely mimic physiological gating produced by muscarinic agonists. The αk effects are general and are similar in atria from adult guinea pig, neonatal rat, and chick embryo. The hydrophilic βgamma; from transducin has no effect while hydropho-bic βgamma; from brain, hRBCs, or retina has effects at nanomolar concentrations which in our hands cannot be disSociated from detergent effects. An anti-αk monoclonal antibody blocks muscarinic activation, supporting the concept that the physiological mediator is the a subunit not the βgamma; dimer. The techniques of molecular biology are now being used to specify G protein gating. A "bacterial" αi-3 expressed in Escherichia coli using a pT7 expression system mimics the gating produced by hRBC αk. © 1990 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.