Author:
Avila Guillermo,Medina Irma M.,Jiménez Esperanza,Elizondo Guillermo,Aguilar Citlalli I.
Abstract
Transforming growth factors-β (TGF-βs) are essential to the structural remodeling seen in cardiac disease and development; however, little is known about potential electrophysiological effects. We hypothesized that chronic exposure (6–48 h) of primary cultured neonatal rat cardiomyocytes to the type 1 TGF-β (TGF-β1, 5 ng/ml) may affect voltage-dependent Ca2+ channels. Thus we investigated T- ( ICaT) and L-type ( ICaL) Ca2+ currents, as well as dihydropyridine-sensitive charge movement using the whole cell patch-clamp technique and quantified CaV1.2 mRNA levels by real-time PCR assay. In ventricular myocytes, TGF-β1 did not exert significant electrophysiological effects. However, in atrial myocytes, TGF-β1 reduced both ICaL and charge movement (55% at 24–48 h) without significantly altering ICaT, cell membrane capacitance, or channel kinetics (voltage dependence of activation and inactivation, as well as the activation and inactivation rates). Reductions of ICaL and charge movement were explained by concomitant effects on the maximal values of L-channels conductance ( Gmax) and charge movement (Qmax). Thus TGF-β1 selectively reduces the number of functional L-channels on the surface of the plasma membrane in atrial but not ventricular myocytes. The TGF-β1-induced ICaL reduction was unaffected by supplementing intracellular recording solutions with okadaic acid (2 μM) or cAMP (100 μM), two compounds that promote L-channel phosphorylation. This suggests that the decreased number of functional L-channels cannot be explained by a possible regulation in the L-channels phosphorylation state. Instead, we found that TGF-β1 decreases the expression levels of atrial CaV1.2 mRNA (70%). Thus TGF-β1 downregulates atrial L-channel expression and may be therefore contributing to the in vivo cardiac electrical remodeling.
Publisher
American Physiological Society
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology
Cited by
41 articles.
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