Expression of calcium channel transcripts in the zebrafish heart: dominance of T-type channels

Abstract

Calcium channels are necessary for cardiac excitation-contraction (E-C) coupling, but Ca channel composition of fish hearts is still largely unknown. To this end, we determined transcript expression of Ca channels in the heart of zebrafish (), a popular model species. Altogether, 18 Ca channel α-subunit genes were expressed in both atrium and ventricle. Transcripts for 7 L-type (Ca1.1a, Ca1.1b, Ca1.2, Ca1.3a, Ca1.3b, Ca1.4a, Ca1.4b), 5 T-type (Ca3.1, Ca3.2a, Ca3.2b, Ca3.3a, Ca3.3b) and 6 P/Q-, N- and R-type (Ca2.1a, Ca2.1b, Ca2.2a, Ca2.2b, Ca2.3a, Ca2.3b) Ca channels were expressed. In the ventricle, T-type channels formed 54.9%, L-type channels 41.1% and P/Q-, N- and R-type channels 4.0% of the Ca channel transcripts. In the atrium, the relative expression of T-type and L-type Ca channel transcripts was 64.1% and 33.8%, respectively (others accounted for 2.1%). Thus, at the transcript level, T-type Ca channels are prevalent in zebrafish atrium and ventricle. At the functional level, peak densities of ventricular T-type () and L-type () Ca current were 6.3±0.8 and 7.7±0.8 pA pF, respectively. mediated a sizeable sarcolemmal Ca influx into ventricular myocytes: the increment in total cellular Ca content via was 41.2±7.3 µmol l, which was 31.7% of the combined Ca influx (129 µmol l) via and (88.5±20.5 µmol l). The diversity of expressed Ca channel genes in zebrafish heart is high, but dominated by the members of the T-type subfamily. The large ventricular is likely to play a significant role in E-C coupling.

Zebrafish Heart Failure Models

“…In human ventricular cardiomyocytes, the majority of calcium responsible for muscle contraction comes from the intracellular stores of the sarcoplasmic reticulum (SR), whereas in zebrafish SR calcium release is limited, accounting for only a fraction of the calcium transient ( Bovo et al, 2013 ). In zebrafish, the main source of calcium for muscle contraction is extracellular calcium, which enters mainly via sarcolemmal T-type calcium channels ( Vornanen and Hassinen, 2016 ; Haverinen et al, 2018 ). In humans, the sarcolemmal calcium current necessary for calcium-induced calcium release occurs via L-type calcium channels, whereas significant expression of T-type calcium channels is lacking ( Gaborit et al, 2007 ).…”

Mapping Calcium Dynamics in the Heart of Zebrafish Embryos with Ratiometric Genetically Encoded Calcium Indicators

“…The zebrafish heart is composed of an atrium and a ventricle, with many anatomical differences with the mammalian heart. However, it has been argued that the zebrafish heart physiology, heart rate (HR), and action potential, while showing some channel expression differences, are more similar to those of the human than other animal models, such as the mouse [5][6][7][8][9][10][11]. For all these reasons, the zebrafish is increasingly considered a model in cardiovascular research in phenotype-based drug and genetic screenings [12][13][14][15].…”

Utility of Zebrafish Models of Acquired and Inherited Long QT Syndrome

“…Biophysical characterization and selective drug blockade under voltage clamp conditions, allowed these authors to examine Na + , Ca 2+ , and K + in isolated zebrafish ventricular myocytes. These studies demonstrated key roles for voltage-gated Na + channels in the action potential upstroke, and L-type and T-type Ca 2+ channels in the maintenance of the plateau phase ( Nemtsas et al, 2010 ; Zhang et al, 2010 ); the prominent role of the latter being somewhat different from that in the adult mammalian ventricle ( Haverinen et al, 2018 ). Other studies suggest a prominent role for Na + -Ca 2+ exchange current at depolarized voltages during the plateau phase ( Zhang et al, 2010 ).…”