Potassium channels in neurons are linked by guanine nucleotide binding (G) proteins to numerous neurotransmitter receptors. The ability of G _o , the predominant G protein in the brain, to stimulate potassium channels was tested in cell-free membrane patches of hippocampal pyramidal neurons. Four distinct types of potassium channels, which were otherwise quiescent, were activated by both isolated brain G _o and recombinant G _o α. Hence brain G _o can couple diverse brain potassium channels to neurotransmitter receptors.

The signaling pathways by which β-adrenergic agonists modulate voltage-dependent cardiac sodium currents are unknown, although it is likely that adenosine 3′5′-monophosphate (cAMP) is involved. Single-channel and whole-cell sodium currents were measured in cardiac myocytes and the signal transducing G protein G _s was found to couple β-adrenergic receptors to sodium channels by both cytoplasmic (indirect) and membrane-delimited (direct) pathways. Hence, G _s can act on at least three effectors in the heart: sodium channels, calcium channels, and adenylyl cyclase. The effect on sodium currents was inhibitory and was enhanced by membrane depolarization. During myocardial ischemia the sodium currents of depolarized cells may be further inhibited by the accompanying increase in catecholamine levels.

Ion channels alternate stochastically between two functional states, open and closed. This gating behavior is controlled by membrane potential or by the binding of neurotransmitters in voltage- and ligand-gated channels, respectively. Although much progress has been made in defining the structure and function of the ligand-binding cores and the voltage sensors, how these domains couple to channel opening remains poorly understood. Here we show that the M3 transmembrane segments of the NMDA receptor allosterically interact with both the ligand-binding cores and the channel gate. It is proposed that M3 functions as a transduction element whose conformational change couples ligand binding with channel opening. Furthermore, amino acid homology between glutamate receptor M3 segments and the equivalent S6 or TM2 segments in K⁺channels suggests that ion channel activation and gating are both structurally and functionally conserved.