Adrenergic stimulation of Na/K pump current in adult rat cardiac myocytes in short-term culture.
Passive membrane properties, steady-state Na/K pump current (Ip) and modulation of Ip by adrenergic agonists were studied with patch-clamp techniques in adult rat ventricular myocytes that were freshly isolated or maintained in culture for 1-4 days. Freshly isolated (day 0) myocytes had a 1.7-1.8 times smaller specific membrane resistance compared with that of cells on any day in culture. From day 0 to 4 there was a progressive decrease in cell capacitance (-17.6 +/- 0.8 pF/day) without a parallel decline in cell dimensions. The pump current density (1.55 pA/pF) was stable over the 0-4 days in culture. In rod-shaped myocytes norepinephrine (NE) and isoproterenol (ISO) stimulated Ip in a dose-dependent manner, with an apparent affinity of 36 +/- 8 and 1.5 +/- 0.4 nM, and maximum stimulation of 0.65 +/- 0.02 and 0.57 +/- 0.02 pA/pF, respectively. Nadolol suppressed this effect, suggesting that it was mediated by beta-adrenergic receptor activation. An inverse relationship was found between steady-state Ip and the stimulation of Ip by NE. In contrast to what was shown in guinea pig cardiac myocytes, in rat myocytes isoproterenol stimulation of Ip was not increased by intracellular [Ca] and it did not change the Ip-membrane potential relation. These results show that in adult rat cardiac myocytes NE and ISO are potent stimulators of Na/K pump activity, and this effect may be studied using rat myocytes maintained in short-term culture.
Stimers
J R
JR
Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Dobretsov
M
M
D000322:Adrenergic Agonists / Q000494:pharmacology*; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D002478:Cells, Cultured; D004789:Enzyme Activation; D007424:Intracellular Fluid / Q000187:drug effects / Q000201:enzymology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects* / Q000378:metabolism
D000322:Adrenergic Agonists; D015221:Potassium Channels; D015222:Sodium Channels; D000254:Sodium-Potassium-Exchanging ATPase; D007545:Isoproterenol; D009638:Norepinephrine