Abstract
The effect of tyrosine protein kinase inhibitors on the swelling-induced chloride current (I Cl-swelling of dog atrial myocytes was studied using the whole-cell patch-clamp recording technique. Currents were measured during hyperpolarizing voltage ramps with potassium currents blocked by cesium. Osmolarity was varied using mannitol. Exposure to hypotonic solution (≈249 mosmol/kg) activated I Cl-swelling. Hypertonic solution (≈ 363mosmol/kg) was used to shrink swollen cells and turn off I Cl-swelling. In studies on the acute effect of tyrosine protein kinase inhibitors each cell was swollen three separate times. Control, treatment, and washout I Cl-swelling were compared. Genistein (50–80 μM) prevented reactivation of I Cl-swelling without affecting cell size. The effect of genistein partially subsided upon washout. The effect of genistein on I Cl-swelling was not mimicked by 80 μM daidzein, a related compound that does not inhibit tyrosine protein kinases. When intracellular adenosine 5′-0-(3-thiotriphosphate (ATP[γS]) was used, genistein did not prevent the reactivation of I Cl-swelling. Intracellular ATP[γS] did not result in a persistent activation of I Cl-swelling when cell size was returned to control. Acute exposure to 1 μM herbimycin A or 100 μM tyrphostin 51 did not prohibit the activation of I Cl-swelling. A 24-h exposure to 1 μM herbimycin A did inhibit I Cl-swelling. The results provide important clues regarding the activation mechanism for I Cl-swelling and suggest that a tyrosine protein phosphorylation may be necessary, but not sufficient, for activation of I Cl-swelling.
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Sorota, S. Tyrosine protein kinase inhibitors prevent activation of cardiac swelling-induced chloride current. Pflugers Arch. 431, 178–185 (1995). https://doi.org/10.1007/BF00410189
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DOI: https://doi.org/10.1007/BF00410189