Regulation of KCa current by store-operated Ca21 influx depends on internal Ca21 release in HSG cells

Liu, Xibao, Eduardo Rojas, and Indu S. Ambudkar. Regulation of KCa current by store-operated Ca21 influx depends on internal Ca21 release in HSG cells. Am. J. Physiol. 275 (Cell Physiol. 44): C571–C580, 1998.—This study examines the Ca21 influx-dependent regulation of the Ca21-activated K1 channel (KCa) in human submandibular gland (HSG) cells. Carbachol (CCh) induced sustained increases in the KCa current and cytosolic Ca21 concentration ([Ca]i), which were prevented by loading cells with 1,2-bis(2-aminophenoxy)ethane-N,N,N8,N8-tetraacetic acid (BAPTA). Removal of extracellular Ca21 and addition of La31 or Gd31, but not Zn21, inhibited the increases in KCa current and [Ca]i. Ca21 influx during refill (i.e., addition of Ca21 to cells treated with CCh and then atropine in Ca21-free medium) failed to evoke increases in the KCa current but achieved internal Ca21 store refill. When refill was prevented by thapsigargin, Ca21 readdition induced rapid activation of KCa. These data provide further evidence that intracellular Ca21 accumulation provides tight buffering of [Ca]i at the site of Ca21 influx (H. Mogami, K. Nakano, A. V. Tepikin, and O. H. Petersen. Cell 88: 49–55, 1997). We suggest that the Ca21 influx-dependent regulation of the sustained KCa current in CCh-stimulated HSG cells is mediated by the uptake of Ca21 into the internal Ca21 store and release via the inositol 1,4,5-trisphosphate-sensitive channel.