Characterization of nifedipine-resistant calcium current in neonatal rat ventricular cardiomyocytes

Abstract

Calcium current was recorded from ventricular cardiomyocytes of rats at various stages of postnatal development using the whole cell patch-clamp technique. In cultured 3-day-old neonatal cells, the current carried by Ca(2+) or Ba(2+) (5 mM) was not completely inhibited by 2 microM nifedipine. A residual current was activated in the same voltage range as the L-type, nifedipine-sensitive Ca(2+) current, but its steady-state inactivation was negatively shifted by 16 mV. This nifedipine-resistant calcium current was not further inhibited by other organic calcium current antagonists such as PN200-110, verapamil, and diltiazem nor by nickel, omega-conotoxin, or tetrodotoxin. It was completely blocked by cadmium and increased by isoproterenol and forskolin. This current was >20% of total calcium current in ventricular myocytes freshly isolated from neonatal rats, and it decreased during postnatal maturation, disappearing at the adult stage. This suggests that this current could be caused by an isoform of the L-type calcium channel expressed in a way that reflects the developmental stage of the rat heart.

Myofibroblasts Electrotonically Coupled to Cardiomyocytes Alter Conduction: Insights at the Cellular Level from a Detailed In silico Tissue Structure Model

“…In contrast to this behavior, dense monolayer cultures of CMCs are quiescent and become spontaneously active only when coupled to a sufficient number of MFBs (Miragoli et al, 2007). To accommodate for this difference, the window current was decreased by shifting the activation and deactivation rate constants of the activation gate d by 6 mV toward more positive potentials which is in accordance to experimental data (Xiao et al, 1997; Pignier and Potreau, 2000). The modified rate constants of the gating variables d and f are given by Equations (2–5):…”

Pharmacological preconditioning by diazoxide downregulates cardiac L‐type Ca2+ channels

“…Likewise, nifedipine during reperfusion reduced LDH loss to 46 ± 10% of control values ( n = 3). For both LDH and infarction area measurements, 30 nM nifedipine was used to block L‐type Ca 2+ current in adult rat ventricular myocytes to 50% of the control value (Pignier and Potreau, 2000). Diazoxide reduced the magnitude of L‐type currents and Ca 2+ channel expression to approximately this level (Figures 1 and 8).…”

Cyclic GMP/PKG-dependent inhibition of TRPC6 channel activity and expression negatively regulates cardiomyocyte NFAT activation

“…Moreover, there is potentially interaction between this modification and calcineurin activity, as Cn increased LTCC current by de-phosphorylating Ser1928 (α1-subunit) [35] one of the PKG targets. In contrast, we found nifedipine at a dose sufficient to block LTCC in NRVM [36] had no impact on ET1-mediated TRPC6 gene or the capacity of SIL to suppress it. This suggests that the TRPC6 positive-feedback loop is largely independent of LTCC activity.…”