Regional expression of L‐type calcium channel subunits during cardiac development

Abstract

The contraction of cardiomyocytes is initiated by the entrance of extracellular calcium through specific calcium channels. Within the myocardium, L-type calcium channels are most abundant. In the heart, the main pore-forming subunit is the ␣1C, although there is a larger heterogeneity on auxiliary ␤ subunits. We have analyzed the distribution pattern of different ␣1C and ␤ subunits during cardiac development by immunohistochemistry. We observed homogeneous expression of ␣1C and ␤ subunits within the early tubular heart, whereas regional differences are observed during the late embryogenesis. ␤2 and ␤4 show differential expression within the embryonic myocardium. ␣1C D1 displays only a transient enhanced expression in the ventricular conduction system. In adult heart, the expression of the different calcium channel subunits analyzed is homogeneous along the entire myocardium except for ␣1C D1 that is practically undetectable. These findings suggest that ␤ subunits might play a major role in conferring calcium handling heterogeneity within the developing embryonic myocardium, while ␣1C subunits might contribute just transiently. Developmental Dynamics 230:131-136, 2004.

Embryonic Stem Cells in Predictive Cardiotoxicity: Laser Capture Microscopy Enables Assay Development

“…In our study, the presence of protein for cardiac alpha subunit of the L-type calcium channel on the sarcolemmal membrane ( Fig. 4) also corroborated the cardiac lineage of these cells (Acosta et al, 2004).…”

Shortening and intracellular Ca2+ in ventricular myocytes and expression of genes encoding cardiac muscle proteins in early onset type 2 diabetic Goto–Kakizaki rats

“…Changing expression of Cacna1h might be a compensatory response to the reductions in heart rate that have been previously reported in young GK rats ). L-type Ca 2+ channels are formed by heteromultimeric complexes of α, β and γ subunits (Acosta et al 2004). The major L-type voltage-gated calcium channels in the heart consist of an α 1C (Ca V 1.2) subunit, usually associated with an auxiliary β subunit (Ca V β2; Meissner et al 2011).…”

Maintenance Of Calcium Homeostasis in Embryonic Stem Cell-Derived Cardiomyocytes

“…In H7 hESC-derived CMs, Ca 2+ transients that were detected at day 17 post-differentiation could be eliminated by the application of 10μM diltiazem, an L-type specific antagonist; this signified the functionality of L-type channels by this time-point (Zhu et al, 2009). Similar to humans, the expression of Ca V 1.2 was also up-regulated from its initial detection at E9.5 when the earliest contractions were observed by about three-fold at E15.5 when the heart has fully matured in mouse embryos; its protein was detected by E12.5 in mouse embryos (Acosta et al, 2004;Xu et al, 2003). In mESCs, patch clamp and Ca 2+ imaging experiments indicated the functional expression of the I Ca, L starting from differentiation day 7, even before the appearance of spontaneous contractions (Kolossov et al, 1998).…”