January 1, 2007Cellular Physiology and Biochemistry
Functional Expression and Inactivation of L-type Ca²⁺ Currents During Murine Heart Development -Implications for Cardiac Ca²⁺ Homeostasis
Key Points
- To investigate the mechanisms driving increased L-type Ca2+ current density and changes in channel inactivation kinetics across murine embryonic and fetal heart development.
- Examined electrophysiological properties of L-type Ca2+ currents (I(CaL)) using the whole-cell patch-clamp technique.
- Sampled ventricular cardiomyocytes from early developmental (E9.5–11.5, n=8–13) and late developmental fetal stages (E16.5–18.5, n=9–14), as well as adult mice.
- Assessed the role of calcium-induced calcium release and sarcoplasmic reticulum stores using 10 µM ryanodine.
- Fast calcium-dependent inactivation kinetics (tau(f)) accelerated significantly in late developmental cardiomyocytes (2.53 ± 1.43 ms, n=9) compared to early developmental cells (5.09 ± 2.19 ms, n=8, p=0.009), while slow voltage-dependent inactivation remained unchanged.
- Late developmental cardiomyocytes displayed higher I(CaL) density (-14 ± 2.26 pA/pF, n=14) than early-stage cells (-10.03 ± 1.43 pA/pF, n=13, p < 0.05), which was accompanied by increased maximal gating charge (Q(max)) with no change in open probability.
- Application of 10 µM ryanodine did not alter tau(f) at either developmental stage, demonstrating that local subsarcolemmal Ca2+ accumulation rather than global bulk Ca2+ release mediates the faster inactivation.
Structured PICO
P
Population
Embryonic ventricular cardiomyocytes of early (E9.5-11.5) and late developmental, fetal (LDS, E16.5-18.5) stages and of adult mice
I
Intervention
Ryanodine (10 microM) application to assess calcium-induced calcium release (CICR)
C
Comparator
Early developmental stage (EDS) cardiomyocytes
O
Outcome
Electrophysiological characteristics of I(CaL) inactivation (fast Ca2+-dependent and slow voltage-dependent inactivation kinetics)surrogate
The acceleration of L-type calcium current inactivation during embryonic heart development is likely driven by increased local subsarcolemmal calcium due to higher channel expression, rather than bulk calcium.
Authors
Discussion
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Implication
Should not change clinical practice; leaves open developmental regulation of I(CaL) inactivation pending human validation.
Cite This Study
Nguemo et al. (2007) studied this question.