Functional expression and regulation of the hyperpolarization activated non-selective cation current in embryonic stem cellderived cardiomyocytes
Abstract
A key feature of the heart is its spontaneous electrical activity, which is under the regulatory control of the autonomic nervous system. The automaticity of the sinus node is due to the diastolic depolarization and the hyperpolarization-activated non-selective cation current If appears to be involved in its generation (DiFrancesco, 1993). The biophysical characteristics of If comprise timedependent activation kinetics, a linear current-voltage (I-V) relationship and voltage-dependent block upon extracellular application of Cs¤. Recently, If has been cloned and shown to display similar structural characteristics to other voltage-gated ion channels (Gauss et al. 1998; Ludwig et al. 1998; Santoro et al. 1998). As also reported for other cyclic nucleotide-gated ion channels, the carboxyl terminal region of If contains a consensus sequence site for cAMPdependent protein kinases (Ludwig et al. 1998). The non-selective cation current If has been detected in cells of the cardiac conductive system of different species such as frog sinus venosus (Bois & Lenfant, 1990), rabbit sino-atrial node (Yanagihara & Irisawa, 1980), rabbit atrioventricular node (DiFrancesco et al. 1980), cat atrium (Zhou & Lipsius, 1992a) and rabbit Purkinje fibres (DiFrancesco & Ferroni, 1983). In addition, If is present during embryonic and perinatal development since the current has been observed in chick embryonic ventricle (Satoh & Sperelakis, 1991), in freshly isolated and cultured ventricular cells from newborn
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