Vasopressin-stimulated Ca2+ influx in rat hepatocytes is inhibited in high-K+ medium.
We examined the effects of K+ substitution for Na+ on the response of hepatocytes to vasopressin, and on the hepatocyte plasma-membrane potential. (1) High K+ (114 mM) had no effect on the initial increase in phosphorylase a activity in response to vasopressin, but abolished the ability of the hormone to maintain increased activity beyond 10 min. With increasing concentrations a decrease in the vasopressin response was first observed at 30-50 mM-K+. (2) High K+ (114 mM) had no effect on basal 45Ca2+ influx, but abolished the ability of vasopressin to stimulate influx. This effect was also first observed at a concentration of 30-50 mM-K+. (3) Increasing K+ had little effect on the plasma-membrane potential until a concentration of 40 mM was reached. With further increases in concentration the plasma membrane was progressively depolarized. (4) Replacement of Na+ with N-methyl-D-glucamine+ depolarized the plasma membrane to a much smaller extent than did replacement with K+, and was also much less effective in inhibiting the vasopressin response. (5) The plasma-membrane potential was restored to near the control value by resuspending cells in normal-K+ medium after exposure to high-K+ medium. The effects of vasopressin on phosphorylase activity were also restored. (6) We conclude that the Ca2+ channels responsible for vasopressin-stimulated Ca2+ influx are closed by depolarization of the plasma membrane.
Savage
A L
AL
Department of Biochemistry, University of Cambridge, U.K.
Biffen
M
M
Martin
B R
BR
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects*; D002478:Cells, Cultured; D003470:Culture Media; D008099:Liver / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials; D010762:Phosphorylase a / Q000378:metabolism; D011188:Potassium / Q000378:metabolism*; D051381:Rats
D015220:Calcium Channels; D003470:Culture Media; D001127:Arginine Vasopressin; D010762:Phosphorylase a; D011188:Potassium