title: [Na]i modulates isoproterenol's effect on Ca permeability in cultured heart cells.
abstract: Isoproterenol (ISO) augments the slow inward Ca current in cardiac muscle cells. We examined the role of intracellular Na (Nai) on ISO-mediated alterations in Ca uptake in cultured chick heart cells. In 140 mM Na medium, 1 microM ISO did not measurably alter 45Ca uptake. When cells were first preincubated in Na-free medium for 5 min and then incubated in control medium with 45Ca, ISO increased 45Ca uptake by 30%. Nifedipine (10 microM), verapamil (1 microM), or dl-propranolol (1 microM) abolished the effect of ISO on 45Ca uptake. CGP 28392 (1 microM), a Ca channel agonist, increased Ca influx in a manner that was augmented by decreased Nai, similar to the ISO response. Neither ISO nor CGP 28392 altered 45Ca uptake when cells preincubated in Na-free medium were further incubated in Na-free medium containing 45Ca. Exposure of cells to Na-free medium or 25 mM K+ medium caused depolarization of the resting membrane potential to approximately -40 mV. In the absence of ISO, the 45Ca uptake in cells preincubated in Na-free or 25 mM extracellular K (Ko) medium was significantly greater than in cells preincubated in control medium. This appeared to be due partly to increased 45Ca uptake via nifedipine-sensitive pathways. These findings support the hypothesis that reduction in Nai concentration ([Na]i) enhances the ISO-induced augmentation of Ca uptake via nifedipine-sensitive pathways (presumably via slow Ca channels), probably by a direct effect on the channels.
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002478:Cells, Cultured; D004563:Electrochemistry; D007425:Intracellular Membranes / Q000378:metabolism*; D007473:Ion Channels / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009994:Osmolar Concentration; D011188:Potassium / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D007473:Ion Channels; D011725:Pyridines; C040525:CGP 28392; D012964:Sodium; D007545:Isoproterenol; D011188:Potassium; D002118:Calcium