ATP and vasopressin activate a single type of store-operated Ca2+ channel, identified by patch-clamp recording, in rat hepatocytes.
Hepatocytes are highly polarised epithelial cells that mediate a large number of metabolic pathways, the transcellular movement of numerous ions and metabolites, and the secretion of proteins from both basal and canalicular membrane regions. Hormone-induced changes in the concentration of intracellular Ca2+ play a central role in regulating these functions. Store-operated Ca2+ channels (SOCs) and other Ca2+-permeable channels in the plasma membrane which are activated by hormones are essential for regulating the amount of Ca2+ in the hepatocyte in order to allow these Ca2+ signalling processes to occur. However, the properties of hormone-activated Ca2+ channels in hepatocytes and in other epithelial cells are not well defined. In this study, we have investigated SOCs in cultured rat hepatocytes by patch-clamp recording using IP3 and hormones as activators. We show that IP3 activates a single type of SOC, which, on the basis of its high selectivity for Ca2+ over Na+, inhibition by La3+ and 2-aminoethyl diphenylborate (2-APB), and the time course of fast inactivation, is very similar to CRAC channel in mast cells and lymphocytes. Moreover, a current (ISOC) with properties identical to those of the IP3-activated current can be activated by physiological concentrations of ATP and vasopressin. It is concluded that SOCs with properties similar to those of CRAC channel are present in hepatocytes, highly differentiated primary cells, and these channels can be activated by hormones under conditions close to physiological.
Rychkov
Grigori Y
GY
School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia 5005, Australia. grigori.rychkov@adelaide.edu.au
Litjens
Tom
T
Roberts
Michael L
ML
Barritt
Greg J
GJ
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D013997:Time Factors; D014667:Vasopressins / Q000378:metabolism*
D015220:Calcium Channels; D014667:Vasopressins; D000255:Adenosine Triphosphate