T-type calcium currents in rat cardiomyocytes during postnatal development: contribution to hormone secretion

Abstract

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.

Molecular Physiology of Low-Voltage-Activated T-type Calcium Channels

“…T-type currents are readily detectable in neonatal hearts, increase slightly to a peak between postnatal days 4 and 8, then decline slowly to a steady-state (236,246). In other studies T-type currents were only detected in neonatal rats, disappearing by postnatal day 21 (236).…”

“…This suggests that nickel (Ͻ100 M) can be used to implicate Ca v 3.2 channel expression. Expression in atrium appears to be species specific: Ca v 3.1 appears to predominate in rat and mice (91,236), while in guinea pigs it is Ca v 3.2 (323). In fact, careful measurement of the nickel dose response in guinea pig atrium revealed a biphasic response, with 80% of the channels being blocked with an apparent IC 50 of 23 M, while 20% of the channels were inhibited with an IC 50 of 1,350 M. Rabbit and cat SAN cells appear to predominantly express Ca v 3.2 channels.…”

“…A role for T-type channels in triggering atrial natriuretic peptide (ANP) secretion has been inferred from the effects of mibefradil (236,434). Evidence that mibefradil acted on T-type channels was provided by the observation that L-type blockers were much less potent blockers, or stimulated ANP secretion.…”

T-type channels-secretion coupling: evidence for a fast low-threshold exocytosis

“…T-type channels are known to play also a main role in the control of hormone release from cells lacking secretory vesicles and exocytotic mechanisms. This aspect, however, will not be treated in this study because there are already excellent articles and up-to-date reviews covering this issue [40,55,58,61].…”

Pathophysiological Significance of T-type Ca2+ Channels: Transcriptional Regulation of T-type Ca2+ Channel — Regulation of CACNA1H by Neuron-Restrictive Silencer Factor

“…T-type Ca 2+ current in adult heart is restricted to the conduction system. In contrast, T-type Ca 2+ current is recorded in ventricular myocyte from embryonic and neonatal hearts (3). In addition, the analyses of T-type Ca 2+ current in several models of cardiac hypertrophy or myocardial infarction suggest the increased or de novo functional expression of T-type channel in the ventricle (4).…”