title: Phenylephrine-induced stimulation of Na+/Ca2+ exchange in rat ventricular myocytes.
abstract: OBJECTIVE
  The effect of an alpha-adrenergic agonist, phenylephrine, on the Na+/Ca2+ exchange current in rat ventricular myocytes was investigated.
  
  
  METHODS
  The Na+/Ca2+ exchange current was measured at room temperature in rat ventricular myocytes as the whole-cell current induced by addition of extracellular Na+ and Ca2+, while blocking Na+ current by setting the holding potential at -30 mV, K+ currents by intracellular Cs+, TEA+ and by extracellular Ba2+, Ca2+ current by nifedipine and Na+ pump current by ouabain or by 0 extracellular K+.
  
  
  RESULTS
  Under these experimental conditions, application of external Na+ and Ca2+ induced a current which was further increased by phenylephrine. Phenylephrine (80 microM) increased the current by up to 31.0 +/- 5.4% of control at all membrane potentials tested both below and above the reversal potential. The reversal potential (+21.0 +/- 3.2 mV), which corresponded with the theoretical reversal potential for the Na+/Ca2+ exchange current under our ionic conditions (+21.3 mV), was not changed by phenylephrine (+23.2 +/- 4.1 mV). Applying phenylephrine in the absence of Na+/Ca2+ exchange (0 Na+e, 0 Ca2+e) did not change the current. The effect was resistant to propranolol, a beta-adrenergic blocker, but prevented by prazosin, an alpha-receptor antagonist, by neomycin, an inhibitor of phospholipase C, and by chelerythrine, a selective inhibitor of protein kinase C. Phorbol 12-myristate 13-acetate failed to stimulate the current. The effect remained similar under conditions of high (HEPESi = 5 mM) and low (HEPESi = 0.5 mM) intracellular pH buffering.
  
  
  CONCLUSIONS
  Our data indicate that phenylephrine stimulates the Na+/Ca2+ exchange, both in the forward and the reverse modes, probably via a protein kinase C-dependent pathway.
authors.affiliation: Centre for Experimental Surgery and Anaesthesiology, Katholieke Universiteit Leuven, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Stengl
authors.forename: K
authors.initials: K
authors.lastname: Mubagwa
authors.forename: E
authors.initials: E
authors.lastname: Carmeliet
authors.forename: W
authors.initials: W
authors.lastname: Flameng
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000470:Alkaloids; D000818:Animals; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D009355:Neomycin / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010617:Phenanthridines / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D019831:Sodium-Calcium Exchanger / Q000187:drug effects*; D013268:Stimulation, Chemical; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D000470:Alkaloids; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D010617:Phenanthridines; D011500:Protein Synthesis Inhibitors; D019831:Sodium-Calcium Exchanger; D010656:Phenylephrine; D010042:Ouabain; D011433:Propranolol; C016299:chelerythrine; D011493:Protein Kinase C; D010738:Type C Phospholipases; D009355:Neomycin; D013755:Tetradecanoylphorbol Acetate; D011224:Prazosin