Anomalous increase of Ca2+ current by high concentration K+ stimulation in whole cell clamped GH3 cells

We examined the effect of high concentration K+ (50 mM K+) stimulation to neurosecretory GH3 cells under voltage clamp control and unexpectedly found a considerable increase in the inward current evoked by depolarizing pulses. This augmented current was present in Na+-free solution containing Ca2+, tetraethylammonium+ and tetrodotoxin and showed similarity in its voltage dependence to the Ca+ channel current in the control (5 mM K+) solution. The augmented current was significantly reduced by Ca2+ channel blockers, Co2+ (5 mM) and nifedipine (2.5 microM), and was increased by the raise of external Ca2+ concentration. Correspondingly, Quin-2 experiments in GH3 cells showed that the rise in cytosolic free Ca2+ concentration in response to high K+ stimulation was suppressed by the same concentration of nifedipine. These data suggest that, in addition to its depolarizing effect, high K+ may modify voltage-sensitive Ca2+ channels such that they exhibit increased permeability although their voltage dependence of activation and pharmacological sensitivity remain largely unchanged.