L-type Ca 2+ channels of the embryonic mouse heart

• Published in: European journal of pharmacology Vol. 447; no. 2; pp. 279 - 284
• Main Authors: Klugbauer, Norbert, Welling, Andrea, Specht, Verena, Seisenberger, Claudia, Hofmann, Franz
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 2002
• Subjects: Ca 2+ channel; Ca v1.3; Dihydropyridine; Embryo, mouse; Heart; L-type Ca 2+ channel; voltage-gated; Heart; Ca v1.3; Embryo, mouse; Ca 2+ channel; Dihydropyridine; L-type Ca 2+ channel
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(02)01850-2

In the heart, where Ca 2+ influx across the sarcolemma is essential for contraction, L-type Ca 2+ channels represent the major entry pathway of Ca 2+. Mice with a homozygous deletion of the L-type Ca v1.2 Ca 2+ channel gene die before day 14.5 p.c. Electrophysiological and pharmacological investigations on Ca v1.2−/− cardiomyocytes demonstrated that contractions depended on the influx of Ca 2+ through an L-type-like Ca 2+ channel. We analyzed now the expression pattern of various L-type Ca 2+ channels. Amplification of the alternative exons 1a and 1b revealed that embryonic cardiac cells express both Ca v1.2a and Ca v1.2b subunits. Reverse transcriptase-polymerase chain reaction (RT-PCR) amplifications indicated the expression of Ca v1.1 and Ca v1.3 in about a 1:10 ratio in Ca v1.2−/− embryos. Two different amino termini of the Ca v1.3 cDNA were found in the embryonic heart, which both gave rise to functional channels. Ca v1.3(1a) and Ca v1.3(1b) channels have similar current kinetics and voltage-dependencies as described for Ca v1.3 8A channels [J. Biol. Chem. 276 (2001) 22100], but the properties of Ca v1.3(1a) or Ca v1.3(1b) channels are different from that of the L-type-like current in Ca v1.2−/− cardiomyocytes. The I Ba of Ca v1.3(1a) was blocked by the dihydropyridine nisoldipine with an IC 50 value of 0.13 μM at a holding potential of −80 mV. In embryonic Ca v1.2+/+ cardiomyocytes, I Ba was blocked by nisoldipine with an IC 50 value of 0.1 μM. Although the expressed Ca v1.3 channel has a similar affinity for nisoldipine as Ca v1.2+/+ cardiomyocytes, the L-type-like Ca 2+ channel found in Ca v1.2+/+ and −/− cardiomyocytes is not identical with the new Ca v1.3 splice variants.