High-conductance K+ channel in pancreatic islet cells can be activated and inactivated by internal calcium

Abstract
The Ca2+-activated K+ channel in rat pancreatic islet cells has been studied using patch-clamp single-channel current recording in excised inside-out and outside-out membrane patches. In membrane patches exposed to quasi-physiological cation gradients (Na+ outside, K+ inside) large outward current steps were observed when the membrane was depolarized. The single-channel current voltage (I/V) relationship showed outward rectification and the null potential was more negative than −40 mV. In symmetrical K+-rich solutions the single-channelI/V relationship was linear, the null potential was 0 mV and the singlechannel conductance was about 250 pS. Membrane depolarization evoked channel opening also when the inside of the membrane was exposed to a Ca2+-free solution containing 2mm EGTA, but large positive membrane potentials (70 to 80 mV) were required in order to obtain open-state probabilities (P) above 0.1. Raising the free Ca2+ concentration in contact with the membrane inside ([Ca2+]i) to 1.5×10−7 m had little effect on the relationship between membrane potential andP. When [Ca2+]i was increased to 3×10−7 m and 6×10−7 m smaller potential changes were required to open the channels. Increasing [Ca2+]i further to 8×10−7 m again activated the channels, but the relationship between membrane potential andP was complex. Changing the membrane potential from −50 mV to +20 mV increasedP from near 0 to 0.6 but further polarization to +50 mV decreasedP to about 0.2. The pattern of voltage activation and inactivation was even more pronounced at [Ca2+]i=1 and 2 μm. In this situation a membrane potential change from −70 to +20 mV increasedP from near 0 to about 0.7 but further polarization to +80 mV reducedP to less than 0.1. The high-conductance K+ channel in rat pancreatic islet cells is remarkably sensitive to changes in [Ca2+]i within the range 0.1 to 1 μm which suggests a physiological role for this channel in regulating the membrane potential and Ca2+ influx through voltage-activated Ca2+ channels.