RECEPTOR-INDEPENDENT ACTIVATION OF ATRIAL MUSCARINIC POTASSIUM CHANNELS IN THE ABSENCE OF NUCLEOTIDES

The removal of nucleotides from the solution bathing the inner face of excised patches of frog atrial membranes was found to activate muscar inic K+ channels in the absence of agonists, Channel activation was al so observed in Mg2+-free solutions and blocked by low (0.1-10 mu M) co ncentrations Of GDP or GTP. After full activation was achieved, channe l openings were abolished by the application of GDP-bound G alpha(i2), but were not affected by exogenous G beta gamma dimers, suggesting th at effector activation is a consequence of the liberation of beta gamm a subunits from endogenous G proteins. The process of channel activati on in the absence of nucleotides seems to be receptor-independent, bec ause it is not influenced by muscarinic receptor agonists and antagoni sts or by treatment with uncoupling agents such as pertussis toxin or N-ethyl maleimide, Taken together, these results suggest that the loss of GDP from the G protein nucleotide binding site promotes its uncoup ling from receptors and destabilizes the G alpha((empty))beta gamma he terotrimer. Therefore, the nucleotide-free form of G proteins has some of the characteristics of the GTP-bound, activated form.