Differential Blocking Action of Dihydropyridine Ca2+ Antagonists on a T-Type Ca2+ Channel (α1G) Expressed in Xenopus Oocytes

Abstract

Recent reports show that efonidipine, a dihydropyridine Ca2+ antagonist, has blocking action on T-type Ca2+ channels, which may produce favorable actions on cardiovascular systems. However, the effects of other dihydropyridine Ca2+ antagonists on T-type Ca2+ channels have not been investigated yet. Therefore, in this study, we examined the effects of dihydropyridine compounds clinically used for treatment of hypertension on a T-type Ca2+ channel subtype, alpha1G, expressed in Xenopus oocytes. These effects were compared with those on T-type Ca2+ channel. Rabbit L-type (alpha1Calpha2/deltabeta1a) or rat T-type (alpha1G) Ca2+ channel was expressed in Xenopus oocytes by injection of cRNA for each subunit. The Ba currents through expressed channels were measured by conventional 2-microelectrode voltage-clamp methods. Twelve DHPs (amlodipine, barnidipine, benidipine, cilnidipine, efonidipine, felodipine, manidipine, nicardipine, nifedipine, nilvadipine, nimodipine, nitrendipine) and mibefradil were tested. Cilnidipine, felodipine, nifedipine, nilvadipine, minodipine, and nitrendipine had little effect on the T-type channel. The blocks by drugs at 10 microM were less than 10% at a holding potential of -100 mV. The remaining 6 drugs had blocking action on the T-type channel comparable to that on the L-type channel. The blocking actions were also comparable to that by mibefradil. These results show that many dihydropyridine Ca2+ antagonists have blocking action on the alpha1G channel subtype. The action of dihydropyridine Ca2+ antagonists in clinical treatment should be evaluated on the basis of subtype selectivity.

Benidipine reduces albuminuria and plasma aldosterone in mild-to-moderate stage chronic kidney disease with albuminuria

“…18,19 However, it has been reported that the antiproteinuric effects of T-type CCBs are not mediated by angiotensin II inhibition but by blockade of T-type Ca channels in the glomerular arterioles. 6 Furukawa et al 20 surveyed the blocking activity of various CCBs on L-/T-/N-type Ca current in Xenopus oocytes. Although both benidipine and amlodipine exhibited blocking function on both L-and T-type Ca channels, benidipine predominantly blocked the T-type Ca channel, whereas amlodipine predominantly blocked the L-type Ca channel.…”

“…Furthermore, the concentration required for benidipine to exert the inhibitory effect on T-type Ca channels can be achieved at clinically relevant doses of benidipine used for the treatment of hypertension. 20,21 Therefore, benidipine, an L-/T-type CCB, should offer additive benefits over CCB-inhibiting L-type Ca channels, but not T-type Ca channels. Furthermore, T-type Ca channels are distributed in the cardiac sinus node and are closely associated with pacemaking potentials.…”

Blocking T-Type Ca2+ Channels with Efonidipine Decreased Plasma Aldosterone Concentration in Healthy Volunteers

“…Efonidipine antagonizes both T-and L-type Ca 2+ channels with similar affinity and has little effect on the N-, P/Q-, and R-type Ca 2+ channels. On the other hand, nifedipine and nilvadipine antagonize only the L-type channels and have lit-tle effect on the other types of Ca 2+ channels (8,9). Hence, we compared efonidipine, nifedipine and nilvadipine with regard to their characteristic action of T-type Ca 2+ channel antagonism.…”

Renoprotective Effect and Cost-Effectiveness of Using Benidipine, a Calcium Channel Blocker, to Lower the Dose of Angiotensin Receptor Blocker in Hypertensive Patients with Albumiuria

“…The renoprotective effects of angiotensin receptor blockers (ARBs) and angiotensinconverting enzyme inhibitors (ACEIs) have been demonstrated (2-4). As a result, both have been recommended as (8,9) by the blockade of T-and L-type calcium channels (10,11), both of which exist at the site of the efferent artery (12). In this study, we evaluate the effects of two different therapeutic strategies using ARBs and benidipine on BP and urinary albumin excretion (UAE), as well as the costeffectiveness of each, in hypertensive patients with albuminuria.…”