MODULATION OF M-CURRENT BY INTRACELLULAR CA2+

I(M) is a voltage- and time-dependent K+ current that is suppressed by muscarinic receptor activation. I(M) augmentation following agonist washout was blocked by heavily buffering [Ca2+]i using BAPTA. Although I(M) is not primarily Ca2+ dependent, small increases in [Ca2+]i by photolysis of the "caged" Ca2+ chelator nitr-5 or by evoking action potentials augmented, while larger increases inhibited, I(M). Raising [Ca2+]i for prolonged periods, by nitr-5 photolysis, reduced its sensitivity to agonist, leaving a poorly reversible response. These results suggest that I(M) can be regulated by physiologically relevant changes in [Ca2+]i, placing I(M) in a unique position to modulate cell excitability.