SHIMIZU Tatsuya
   Department   Research Institutes and Facilities, Research Institutes and Facilities
   Position   Professor
Article types Original article
Language English
Peer review Non peer reviewed
Title Selectivity of felodipine for depolarized ventricular myocytes: a study at the single-cell level.
Journal Formal name：European journal of pharmacology
Abbreviation：Eur J Pharmacol
ISSN code：(0014-2999)0014-2999(Linking)
Domestic / ForeginForegin
Volume, Issue, Page 319(2-3),pp.355-63
Author and coauthor Kohmoto O†, Shimizu T, Sugishita K, Kinugawa K, Takahashi T, Serizawa T
Publication date 1997/01
Summary We studied the effects of felodipine (a second-generation dihydropyridine Ca2+ channel blocker) on excitation-contraction coupling (E-C coupling) in single isolated guinea-pig ventricular myocytes, using the whole-cell perforated patch-clamp technique or the Ca indicator, indo-1. Felodipine inhibited both L-type Ca2+ channel currents (ICa) and cell contractions in a concentration-dependent manner (10 pM to 100 nM) when we used a holding potential of -80 mV or -40 mV. The potency of felodipine was sharply dependent on a holding potential. Namely, use of a more depolarized holding potential markedly increased the potency of felodipine for inhibition of ICa and cell contraction. Next we current-clamped cells and obtained the resting membrane potential of -82 +/- 8 mV. When cells were current-injected at 0.1 Hz, exposure to 10 nM felodipine slightly but significantly diminished the amplitude of cell contractions (7.2 +/- 1.6 to 6.7 +/- 1.7 microns, P < 0.05) within 10 min. When cells were field stimulated, exposure of cells to 10 nM felodipine also slightly diminished the amplitude of cell shortening (5.1 +/- 2.0 to 4.6 +/- 1.9 microns, P < 0.05) and [Ca2+]i transients. We observed clear voltage-dependent blockade of E-C coupling by felodipine in ventricular myocytes. Thus, therapeutic concentrations (1-10 nM) of felodipine could inhibit E-C coupling in depolarized ventricular myocytes, which might simulate an ischemic or failing heart.
DOI https://doi.org/10.1016/S0014-2999(96)00867-9
PMID 9042611