Key result
Neonatal T-type calcium current in rat cardiomyocytes is related to the alpha(1G)-subunit and contributes significantly to calcium signaling and atrial natriuretic factor secretion.
This preclinical study identifies the alpha(1G)-subunit as the likely basis for neonatal cardiac T-type calcium currents and demonstrates its role in atrial natriuretic factor secretion.
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Provides mechanistic insight into neonatal rat cardiomyocyte signaling; leaves open relevance to human cardiac development or therapy.
T-type Ca(2+) channels have been suggested to play a role in cardiac automaticity, cell growth, and cardiovascular remodeling. Although three genes encoding for a T-type Ca(2+) channel have been identified, the nature of the isoform(s) supporting the cardiac T-type Ca(2+) current (I(Ca,T)) has not yet been determined. We describe the postnatal evolution of I(Ca,T) density in freshly dissociated rat atrial and ventricular myocytes and its functional properties at peak current density in young atrial myocytes. I(Ca,T) displays a classical low activation threshold, rapid inactivation kinetics, negative steady-state inactivation, slow deactivation, and the presence of a window current. Interestingly, I(Ca,T) is poorly sensitive to Ni(2+) and insensitive to R-type current toxin SNX-482. RT-PCR experiments and comparison of functional properties with recombinant Ca(2+) channel subtypes suggest that neonatal I(Ca,T) is related to the alpha(1G)-subunit. Atrial natriuretic factor (ANF) secretion was measured using peptide radioimmunoassays in atrial tissue. Pharmacological dissection of ANF secretion indicates an important contribution of I(Ca,T) to Ca(2+) signaling during the neonatal period.
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Leuranguer et al. (2000) studied Postnatal development of rat cardiomyocytes. Postnatal development was evaluated on I(Ca,T) density, functional properties, and ANF secretion. Neonatal T-type calcium current in rat cardiomyocytes is related to the alpha(1G)-subunit and contributes significantly to calcium signaling and atrial natriuretic factor secretion.
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