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Cardiovascular Research

Publication date: 1998-06-01
Volume: 38 Pages: 703 - 10
Publisher: Oxford University Press (OUP)

Author:

Stengl, M
Mubagwa, Kanigula ; Carmeliet, Edward ; Flameng, Willem

Keywords:

Adrenergic alpha-Agonists, Adrenergic alpha-Antagonists, Adrenergic beta-Antagonists, Alkaloids, Animals, Benzophenanthridines, Enzyme Inhibitors, Myocardium, Neomycin, Ouabain, Patch-Clamp Techniques, Phenanthridines, Phenylephrine, Phospholipase C, Prazosin, Propranolol, Protein Kinase C, Protein Synthesis Inhibitors, Rats, Sodium-Calcium Exchanger, Stimulation, Chemical, Tetradecanoylphorbol Acetate, Science & Technology, Life Sciences & Biomedicine, Cardiac & Cardiovascular Systems, Cardiovascular System & Cardiology, experimental, heart, electrophysiology, pharmacology, adrenergic agonist, membrane current, myocyte, Na/Ca exchanger, protein kinase, rat, PROTEIN-KINASE-C, CARDIAC SARCOLEMMAL VESICLES, SODIUM-CALCIUM EXCHANGE, HEART-CELLS, GUINEA-PIG, NA+-CA2+ EXCHANGE, PHOSPHOLIPASE-C, ACTIVATION, MECHANISM, CHANNEL, Type C Phospholipases, 1102 Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, 3201 Cardiovascular medicine and haematology

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. CONCLUSION: 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.