G(KAPPA)ASTERISK AND BRAIN G(BETA-GAMMA) ACTIVATE MUSCARINIC K+ CHANNEL THROUGH THE SAME MECHANISM

A pertussis toxin-sensitive G protein (G(K)) links muscarinic cholinergic and A1-purinergic receptors with an inwardly rectifying K+ (K(ACh)) channel in cardiac atrial cell membranes. Although the betagamma subunits of pertussis toxin-sensitive G proteins (G(betagamma)) have been reported to fully activate this channel, it is not known whether exogenously applied G(betagamma) interacts with the K(ACh) channel through the same mechanism as the active subunit of endogenous G(K) (G(K)*). We examined in inside-out patches the relationship between the concentration of GTP and K(ACh) channel activity with or without preactivation of the channels by either GTPgammaS (guanosine 5'-3-O-(thio)triphosphate) or G(betagamma) purified from bovine brain. In the control, K(ACh) channels were activated by intracellular GTP (with acetylcholine in the pipette) in a positive cooperative manner (Hill coefficient approximately 2.5). As the channels were preactivated by GTPgammaS to progressively higher levels, the GTP channel activity relationship shifted more to the left, but the Hill coefficients of the curves remained the same. The same changes were observed when K(ACh) channels were preactivated with brain G(betagamma). These results indicate that endogenous G(K)* and exogenous G(betagamma) share a common molecular mechanism to activate the K(ACh) channel.