Src family tyrosine kinases inhibit single L-type: Ca2+ channel activity in human atrial myocytes

Journal of Molecular and Cellular Cardiology
Frank SchröderKai C Wollert

Abstract

Tyrosine kinases (TKs) are important regulators of the L-type Ca(2+) channel (LTCC) current in various cell types. However, there are no data addressing the role of TKs in the control of single LTCC activity in human atrial cardiac myocytes, where changes in LTCC gating properties have been described in a number of disease states. Single LTCC activity was recorded in isolated human atrial myocytes. The broad-spectrum TK inhibitor genistein and the Src family-selective TK inhibitor PP1 significantly enhanced single LTCC ensemble average current, availability, and open probability; the latter was due to significant increases of mean open time and mode 2 gating. Conversely, the tyrosine phosphatase inhibitor bisperoxo-phenanthroline-vanadate inhibited single LTCC activity, indicating that LTCC gating properties in human atrial myocytes are controlled by TKs and tyrosine phosphatases in a reciprocal fashion. The effects of genistein on single LTCC activity were not affected by stimulation (8Br-cAMP) or inhibition (Rp-8-CPT-cAMPS) of protein kinase A (PKA) or by inhibition of serine/threonine phosphatases types I and IIa (okadaic acid), indicating that TKs inhibit LTCC gating in human atrial myocytes independent of PKA and phosphata...Continue Reading

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Citations

May 9, 2006·Journal of Cardiovascular Pharmacology·Suzanne S ArinsburgHan-Gang Yu
Oct 1, 2009·Journal of Cell Science·Kathryn E TifftKatherine L Wilson
Apr 10, 2010·American Journal of Physiology. Gastrointestinal and Liver Physiology·Gracious R RossHamid I Akbarali
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