VASOPRESSIN INCREASES CYTOSOLIC SODIUM CONCENTRATION IN HEPATOCYTES AND ACTIVATES CALCIUM INFLUX THROUGH CATION-SELECTIVE CHANNELS

A variety of hormonal agonists activate transmembrane Na+ and Ca2+ flu x in hepatocytes, but the responsible mechanisms are poorly understood . We employed microfluorimetric and patch clamp recording techniques i n hepatocytes to determine the effect of the hormone vasopressin on cy tosolic Na+ concentration ([Na+]i) and to identify the transmembrane N a+ transport pathways activated by this agonist. Under basal condition s, [Na+]i, measured using the Na+-sensitive fluorophore sodium-binding benzofuran isophthalate, averaged 12.1 +/- 1.6 mM. Exposure to vasopr essin rapidly increased [Na+]i by 8.3 +/- 0.9 mM. This increase was at tributable to activation of Na+ influx. It occurred in the absence of solutes co-transported with Na+ and was not associated with activation of Na+/H+ antiport. In cell-attached membrane patches, vasopressin ac tivated ion channels that carried inward positive current at the resti ng membrane potential. Further characterization in excised membrane pa tches revealed two classes of ion channels, with conductances of 16.0 +/- 2.8 and 30.9 +/- 3.1 picosiemens, respectively. Single channel cur rents reversed near 0 mV, and ion substitution studies demonstrated th at each channel type was permeable to Na+, Ca2+, and K+ but not Cl-. T hese observations in hepatocytes indicate that vasopressin increases [ Na+]i and activates cation-selective channels, which likely accounts f or vasopressin-activated Na+ and Ca2+ influx.