Effects of external K+ on depletion-induced Ca2+ entry in rat ileal smooth muscle

The effects of K+ on Ca2+ influx after transient depletion of Ca2+ stores with carbachol and long-lasting depletion with thapsigargin or ryanodine were examined in fura-2-loaded rat ileal smooth muscle. After transient depletion of Ca2+ stores, application of Ca2+ caused a rise in [Ca2+](i) and a contraction, both of which were increased with increasing K+ applied simultaneously in the absence of methoxyverapamil, but were decreased in its presence. In tissues, long-lasting depletion of Ca2+ stores treated with thapsigarin or ryanodine, [Ca2+](i) and tension were dose dependently increased by the application of Ca2+ regardless of the absence or presence of methoxyverpamil. These responses were inhibited by K+ replacement of Na+ in a dose-dependent manner and the inhibitory action of K+ was attenuated by increasing extracellular Ca2+. The influx of Mn2+ was much greater in the tissues pretreated with thapsigargin or ryanodine than in untreated tissues. The enhanced Mn2+ influx was inhibited by the replacement of Na+ with K+. These results provide further evidence for the presence of a Ca2+ entry mechanism evoked by the depletion of Ca2+ stores in rat ileal smooth muscle, and suggest that there are two types of Ca2+ entry pathways to refill Ca2+ stores, one sensitive and the other insensitive to Ca2+ channel blockers. Ca2+ entry through the latter pathway is inhibited by increasing external K+, perhaps due to a reduction of the electrochemical gradient for Ca2+ across the plasma membrane.