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+ flux in hepatocytes, but the responsible mechanisms are poorly understood. We employed microfluorimetric and patch clamp recording techniques in hepatocytes to determine the effect of the hormone vasopressin on cytosolic Na+ concentration ([Na+]i) and to identify the transmembrane Na+ transport pathways activated by this agonist. Under basal conditions, [Na+]i, measured using the Na(+)-sensitive fluorophore sodium-binding benzofuran isophthalate, averaged 12.1 +/- 1.6 mM. Exposure to vasopressin rapidly increased [Na+]i by 8.3 +/- 0.9 mM. This increase was attributable 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 activated ion channels that carried inward positive current at the resting membrane potential. Further characterization in excised membrane patches revealed two classes of ion channels, with conductances of 16.0 +/- 2.8 and 30.9 +/- 3.1 picosiemens, respectively. Single channel currents reversed near 0 mV, and ion substitution studies demonstrated that each channel type was permeable to Na+, Ca2+, and K+ but not Cl-. These observations in hepatocytes indicate that vasopressin increases [Na+]i and activates cation-selective channels, which likely accounts for vasopressin-activated Na+ and Ca2+ influx.
Lidofsky
S D
SD
Department of Medicine and Liver Center, University of California, San Francisco 94143-0538.
Xie
M H
MH
Sostman
A
A
Scharschmidt
B F
BF
Fitz
J G
JG
D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008564:Membrane Potentials; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D014667:Vasopressins / Q000494:pharmacology*
D007473:Ion Channels; D014667:Vasopressins; D012964:Sodium; D002118:Calcium