Tyrosine kinase inhibition reduces i f in rabbit sinoatrial node myocytes |
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Authors: | Ji-Ying Wu I. S. Cohen |
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Affiliation: | (1) Dept. of Physiology and Biophysics, Health Sciences Center, SUNY at Stony Brook, Stony Brook, NY 11794-8661, USA, US |
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Abstract: | We studied pacemaker current (i f), the inward current activated by hyperpolarization in rabbit sinoatrial (SA) node myocytes, with the permeabilized-patch-clamp technique. The tyrosine kinase inhibitors genistein (50 μM) or herbimycin A (35 μM) reduced the amplitude of i f in response to step hyperpolarizations in the diastolic range of potentials. A two-step voltage-clamp protocol revealed that the reduction in i f is due to a decrease in maximal i f conductance. The observed effects are due to tyrosine kinase inhibition since an inactive analog of genistein did not reduce i f. To further examine the mechanism of action, we added 2 mM chlorophenylthio cAMP (CPTcAMP, a membrane-permeant cAMP analog) to the bathing Tyrode, which increased i f. Genistein still reduced i f in the presence of CPTcAMP. This suggests that the pathway mediating the actions of tyrosine kinase inhibition on i f is independent of cAMP- or protein-kinase-A-mediated phosphorylation. Received: 28 January 1997 / Received after revision: 21 April 1997 / Accepted: 22 April 1997 |
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Keywords: | Tyrosine kinase Genistein Herbimycin Pacemaker current (if) |
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