HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 292/1/H622    most recent 00781.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Avila, G. Articles by Aguilar, C. I. Search for Related Content PubMed PubMed Citation Articles by Avila, G. Articles by Aguilar, C. I.

Transforming growth factor-1 decreases cardiac muscle L-type Ca²⁺ current and charge movement by acting on the Ca_v1.2 mRNA

¹Department of Biochemistry and ²External Section of Toxicology, Cinvestav, México

Submitted 20 July 2006 ; accepted in final form 11 September 2006

Transforming growth factors- (TGF-s) 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- (TGF-1, 5 ng/ml) may affect voltage-dependent Ca²⁺ channels. Thus we investigated T- (I_CaT) and L-type (I_CaL) Ca²⁺ currents, as well as dihydropyridine-sensitive charge movement using the whole cell patch-clamp technique and quantified Ca_V1.2 mRNA levels by real-time PCR assay. In ventricular myocytes, TGF-1 did not exert significant electrophysiological effects. However, in atrial myocytes, TGF-1 reduced both I_CaL and charge movement (55% at 24–48 h) without significantly altering I_CaT, cell membrane capacitance, or channel kinetics (voltage dependence of activation and inactivation, as well as the activation and inactivation rates). Reductions of I_CaL and charge movement were explained by concomitant effects on the maximal values of L-channels conductance (G_max) and charge movement (Q_max). Thus TGF-1 selectively reduces the number of functional L-channels on the surface of the plasma membrane in atrial but not ventricular myocytes. The TGF-1-induced I_CaL 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-1 decreases the expression levels of atrial Ca_V1.2 mRNA (70%). Thus TGF-1 downregulates atrial L-channel expression and may be therefore contributing to the in vivo cardiac electrical remodeling.

calcium channel; atrial fibrillation; muscle disease