Distribution of cAMP-Activated Chloride Current and CFTR mRNA in the Guinea Pig Heart

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Abstract
Guinea pig ventricular myocytes exhibit a Cl−-selective current regulated by the cAMP-dependent pathway. We have investigated the distribution of cAMP-activated Cl− channel current density and cystic fibrosis transmembrane-conductance regulator (CFTR) mRNA in three regions of the guinea pig heart: the atrium, and the epicardium and endocardium of the free wall of the left ventricle. The regional differences in the Cl− current density were investigated in enzymatically isolated myocytes using the whole-cell patch-clamp technique. Forskolin (1 μmol/L) activated Cl−-selective currents in all ventricular myocytes and 21% of atrial myocytes examined. The conductance density, estimated as the outward chord conductance normalized to cell capacitance, was greatest in epicardial myocytes (79.8±8.4 pS/pF, n=21) and significantly lower in endocardial (59.8±9.5 pS/pF, n=22) and atrial (10.9±5.0 pS/pF, n=38) myocytes. The regional differences in CFTR mRNA expression levels were investigated by competitive reverse-transcribed polymerase chain reaction. The regional distribution of the mRNA levels was similar to that of the Cl− conductance density, ie, highest in the epicardium (23 230±1840 molecules/μg total RNA, n=3), significantly lower in endocardium (10 610±780 molecules/μg total RNA, n=3), and lowest in atrium (1450±290 molecules/μg total RNA, n=3). The data indicate that regional differences in CFTR mRNA expression in the guinea pig heart are responsible, at least in part, for the regional differences in cAMP-activated Cl− current density.