Functional Characterization of a Small Conductance GIRK Channel in Rat Atrial Cells

Abstract

Muscarinic K1 (KACh) channels are key determinants of the inhibitory synaptic transmission in the heart. These channels are heterotetramers consisting of two homologous subunits, G-protein-gated inwardly rectifying K1 (GIRK)1 and GIRK4, and have unitary conductance of ;35 pS with symmetrical 150 mM KCl solutions. Activation of atrial KACh channels, however, is often accompanied by the appearance of openings with a lower conductance, suggesting a functional heterogeneity of G-protein-sensitive ion channels in the heart. Here we report the characterization of a small conductance GIRK (scGIRK) channel present in rat atria. This channel is directly activated by Gbg subunits and has a unitary conductance of 16 pS. The scGIRK and KACh channels display similar affinities for Gbg binding and are frequently found in the same membrane patches. Furthermore, Gbg-activated scGIRK channels—like their KACh counterparts—exhibit complex gating behavior, fluctuating among four functional modes conferred by the apparent binding of a different number of Gbg subunits to the channel. The electrogenic efficacy of the scGIRK channels, however, is negligible compared to that of KACh channels. Thus, Gbg subunits employ the same signaling strategy to regulate two ion channels that are apparently endowed with very different functions in the atrial membrane. Originally published Biophysical Journal, Vol. 87, No. 5, Nov 2004