Changes of action potential and L-type calcium channel current of Sprague–Dawley rat ventricular myocytes by different amlodipine isomers

Abstract

To investigate the effects of S- and R-amlodipine (Aml) on action potential (AP) and L-type calcium channel current (ICa-L), the whole-cell patch-clamp technique was used on rat ventricular myocytes to record AP, ICa-L, peak currents, steady-state activation currents, steady-state inactivation currents, and recovery currents from inactivation with S-Aml and R-Aml at various concentrations. Increasing concentrations of S-Aml gradually shortened AP durations (APDs). At concentrations of 0.1, 0.5, 1, 5, and 10 micromol/L, S-Aml blocked 1.5% +/- 0.2%, 25.4% +/- 5.3%, 65.2% +/- 7.3%, 78.4% +/- 8.1%, and 94.2% +/- 5.0% of ICa-L, respectively (p < 0.05), and the half-inhibited concentration was 0.62 +/- 0.12 micromol/L. Current-voltage curves were shifted upward; steady-state activation and inactivation curves were shifted to the left. At these concentrations of S-Aml, the half-activation voltages were -16.01 +/- 1.65, -17.61 +/- 1.60, -20.17 +/- 1.46, -21.87 +/- 1.69, and -24.09 +/- 1.87 mV, respectively, and the slope factors were increased (p < 0.05). The half-inactivation voltages were -27.16 +/- 4.48, -28.69 +/- 4.52, -31.19 +/- 4.17, -32.63 +/- 4.34, and -35.16 +/- 4.46 mV, respectively, and the slope factors were increased (p < 0.05). The recovery times from inactivation of S-Aml were prolonged (p < 0.05). In contrast, R-Aml had no effect on AP and ICa-L (p > 0.05) at the concentrations tested. Thus, only S-Aml has calcium channel blockade activity, whereas R-Aml has none of the pharmacologic actions associated with calcium channel blockers.

Changes in retinal vascular diameters in senior and geriatric cats in association with variation in systemic blood pressure

“…As a calcium channel blocker, the amlodipine relaxes the tone of arterioles and causes a reduction in the arterial BP with a dilating effect on cardiac and vascular smooth muscle cells, thereby improving vascular resistance. 39 Hyperthyroidism causes profound cardiovascular changes and while hypertension does sometimes occur in this condition the major feature of thyrotoxicosis is a profound reduction in systemic vascular resistance. 40 Therefore, the reason for exclusion of the hyperthyroid cats was that in most hypertensive conditions one would expect vascular resistance to be increased, whereas in hyperthyroidism this is decreased.…”

Inhibitory Effect of Cinobufagin on L-Type Ca2+Currents, Contractility, and Ca2+Homeostasis of Isol

“…Ca 2+ channels are found in all excitable cells and are essential for electrical excitability, excitation-contraction coupling, excitation-secretion coupling, and other cellular functions [22]. The development of drugs that block Ca 2+ channels has provided a valuable route for studying channel function, and clinical use of Ca 2+ channel blockers in combating CHD and Ca 2+ overload is rapidly increasing.…”

Pharmacological gating modulation of small- and intermediate-conductance Ca2+-activated K+channels (KCa2.x and KCa3.1)

“…2,3 Another well-known example is the dihydropyridine binding site on Ltype Ca 2C channels (Ca v 1.x): Nifedipine and amlodipine exert complex modulation of voltage-dependent gating parameters resulting in overall decreased Ca 2C -currents at physiological membrane potentials. 4 These negative gating modulators are valuable drugs for the treatment of essential hypertension by their relaxing effect on vascular smooth muscles. However, other dihydropyridines like Bay-K-8644 act as positive gating modulators via the same binding site by primarily shifting the voltage activation curve toward more negative membrane potentials.…”