title: Src family protein tyrosine kinases modulate L-type calcium current in human atrial myocytes.
abstract: In the heart, L-type voltage dependent calcium channels (L-VDCC) provide Ca(2+) for the activation of contractile apparatus. The best described pathway for L-type Ca(2+) current (I(Ca,L)) modulation is the phosphorylation of calcium channels by cAMP-dependent protein kinase A (PKA), the activity of which is predominantly regulated in opposite manner by β-adrenergic (β-ARs) and muscarinic receptors. The role of other kinases is controversial and often depends on tissues and species used in the studies. In different studies the inhibitors of tyrosine kinases have been shown either to stimulate or inhibit, or even have a biphasic effect on I(Ca,L). Moreover, there is no clear picture about the route of activation and the site of action of cardiac Src family nonreceptor tyrosine kinases (Src-nPTKs). In the present study we used PP1, a selective inhibitor of Src-nPTKs, alone and together with different activators of I(Ca,L), and demonstrated that in human atrial myocytes (HAMs): (i) Src-nPTKs are activated concomitantly with activation of cAMP-signaling cascade; (ii) Src-nPTKs attenuate PKA-dependent stimulation of I(Ca,L) by inhibiting PKA activity; (iii) Gα(s) are not involved in the direct activation of Src-nPTKs. In this way, Src-nPTKs may provide a protecting mechanism against myocardial overload under conditions of increased sympathetic activity.
authors.affiliation: Lithuanian University of Health Sciences, Institute of Cardiology, 50009 Kaunas, Lithuania.
authors.forename: Andrius
authors.initials: A
authors.lastname: Bogdelis
authors.forename: Rimantas
authors.initials: R
authors.lastname: Treinys
authors.forename: Edgaras
authors.initials: E
authors.lastname: Stankevičius
authors.forename: Jonas
authors.initials: J
authors.lastname: Jurevičius
authors.forename: V Arvydas
authors.initials: VA
authors.lastname: Skeberdis
mesh_terms: D020746:Calcium Channels, L-Type / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006325:Heart Atria / Q000166:cytology / Q000378:metabolism; D006801:Humans; D032383:Myocytes, Cardiac / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D020746:Calcium Channels, L-Type; D019061:src-Family Kinases; D017868:Cyclic AMP-Dependent Protein Kinases