Regulation of KCa current by store-operated Ca2+ influx depends on internal Ca2+ release in HSG cells

This study examines the Ca2+ influx-dependent regulation of the Ca2+-activated K+ channel (K-Ca) in human submandibular gland (HSG) cells. Carbachol (CCh) induced sustained increases in the K-Ca current and cytosolic Ca2+ concentration ([Ca2+](i)), which were prevented by loading cells with 1,2-bis-(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). Removal of extracellular Ca2+ and addition of La3+ or Gd3+, but not Zn2+, inhibited the increases in K-Ca current and [Ca2+](i). Ca2+ influx during refill (i.e., addition of Ca2+ to cells treated with CCh and then atropine in Ca2+-free medium) failed to evoke increases in the K-Ca current but achieved internal Ca2+ store refill. When refill was prevented by thapsigargin, Ca2+ readdition induced rapid activation of K-Ca. These data provide further evidence that intracellular Ca2+ accumulation provides tight buffering of [Ca2+](i) at the site of Ca2+ influx (H. Mogami, K. Nakano, A. V. Tepikin, and O. H. Petersen. Cell 88: 49-55, 1997). We suggest that the Ca2+ influx-dependent regulation of the sustained K-Ca current in CCh-stimulated HSG cells is mediated by the uptake of Ca2+ into the internal Ca2+ store and release via the inositol 1,4,5-trisphosphate-sensitive channel.