title: Truncation of murine CaV1.2 at Asp 1904 increases CaV1.3 expression in embryonic atrial cardiomyocytes.
abstract: Cardiac CaV1.2 channels play a critical role in cardiac function. It has been proposed that the carboxyl-terminal intracellular tail of the CaV1.2 channel is the target of Ca(2+)-dependent and Ca(2+)-independent regulation of the channel. Recent studies on C-terminal truncated forms of the CaV1.2 channel reported neonatal death, reduced CaV1.2 current, and failure of β-adrenergic stimulation of these channels in ventricular cardiomyocytes (CMs). Here, we used atrial CMs at embryonic day 18.5 that expressed a C-terminal truncated form of the CaV1.2 channel (Stop/Stop). Surprisingly, the atrial CMs showed robust L-type Ca(2+) currents which could be stimulated by forskolin, an activator of adenylyl cyclase. These currents exhibited a left-ward shift in the voltage-dependent activation curve and a reduced sensitivity to the Ca(2+) channel blocker isradipine as compared to currents in wild-type atrial CMs. RT-PCR analysis revealed normal levels of mRNA for the CaV1.2 channel but a twofold increase in the level of mRNA for the CaV1.3 channel in the Stop/Stop atrium as compared to wild-type atrium. A Western blot analysis indicated an increase of CaV1.3 protein in the Stop/Stop atrium. We suggest that, in contrast to Stop/Stop ventricular CMs, Stop/Stop atrial CMs can compensate the functional loss of the truncated CaV1.2 channel with an upregulation of the CaV1.3 channel.
authors: Forschergruppe 923, Institut für Pharmakologie und Toxikologie, TU München, Biedersteiner Str. 29, 80802 München, Germany.
authors: Jie
authors: J
authors: Ding
authors: Katrin
authors: K
authors: Domes
authors: Franz
authors: F
authors: Hofmann
authors: Jörg W
authors: JW
authors: Wegener
mesh_terms: D000200:Action Potentials; D000818:Animals; D001224:Aspartic Acid / Q000235:genetics; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D005318:Fetal Heart / Q000166:cytology; D017353:Gene Deletion; D006325:Heart Atria / Q000166:cytology / Q000378:metabolism; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism; D051379:Mice; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D017434:Protein Structure, Tertiary; D014158:Transcription, Genetic
chemical_list: C514350:CACNA1C protein, mouse; C485995:Cacna1d protein, mouse; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D005576:Colforsin; D001224:Aspartic Acid