Inhibition of T-Type and L-Type Ca2+ Currents by Aranidipine, a Novel Dihydropyridine Ca2+ Antagonist

The effects of aranidipine, a novel dihydropyridine Ca2+ channel antagonist, on membrane currents in guinea pig ventricular myocytes and on action potentials in rabbit sinoatrial node tissue were examined. In myocytes, aranidipine (10 nmol/l to 1 μmol/l) concentration-dependently decreased T-type and L-type Ca2+ currents. Aranidipine (1 μmol/l) had little effect on K+ currents. In the sinoatrial node, 0.1 μmol/l aranidipine increased cycle length, and decreased +v̇max and the slope of the phase 4 depolarization. Thus, inhibition of both T-type and L-type Ca2+ currents by aranidipine may partly explain its potent negative chronotropic activity.

[1]  D. DiFrancesco,et al.  The onset and autonomic regulation of cardiac pacemaker activity: relevance of the f current. , 1995, Cardiovascular research.

[2]  H. Masumiya,et al.  Effects of Ca2+ channel antagonists on sinus node: prolongation of late phase 4 depolarization by efonidipine. , 1997, European journal of pharmacology.

[3]  S. Ertel,et al.  Low-voltage-activated T-type Ca2+ channels. , 1997, Trends in pharmacological sciences.

[4]  H. Masumiya,et al.  Inhibition of myocardial L- and T-type Ca2+ currents by efonidipine: possible mechanism for its chronotropic effect. , 1998, European journal of pharmacology.

[5]  S. Mishra,et al.  Selective inhibition of T-type Ca2+ channels by Ro 40-5967. , 1994, Circulation research.

[6]  A. Noma,et al.  A sustained inward current activated at the diastolic potential range in rabbit sino‐atrial node cells. , 1995, The Journal of physiology.

[7]  W. Rose,et al.  Macroscopic and unitary properties of physiological ion flux through T‐type Ca2+ channels in guinea‐pig heart cells. , 1992, The Journal of physiology.

[8]  H. Kamei,et al.  MPC-1304, another type of dihydropyridine, possessing highly potent vasodilating action. , 1993, European journal of pharmacology.

[9]  H. Masumiya,et al.  Myocardial and vascular effects of efonidipine in vitro as compared with nifedipine, verapamil and diltiazem. , 1996, General pharmacology.

[10]  H. Brown,et al.  Cardiac pacemaking in the sinoatrial node. , 1993, Physiological reviews.

[11]  N. Hagiwara,et al.  Contribution of two types of calcium currents to the pacemaker potentials of rabbit sino‐atrial node cells. , 1988, The Journal of physiology.

[12]  H. Masumiya,et al.  Developmental changes in action potential and membrane currents in fetal, neonatal and adult guinea-pig ventricular myocytes. , 1996, Journal of molecular and cellular cardiology.

[13]  H. Satoh.  Role of T-type Ca2+ channel inhibitors in the pacemaker depolarization in rabbit sino-atrial nodal cells. , 1995, General pharmacology.

[14]  A. Kanda,et al.  Antihypertensive Effects of MPC-1304, a Novel Calcium Antagonist, in Experimental Hypertensive Rats and Dogs , 1992, Journal of cardiovascular pharmacology.

[15]  W. Rose,et al.  Macroscopic and unitary properties of physiological ion flux through L‐type Ca2+ channels in guinea‐pig heart cells. , 1992, The Journal of physiology.

[16]  Y. Nakamura,et al.  Synthesis of asymmetric 4-aryl-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylates with vasodilating and antihypertensive activities. , 1986, Chemical & pharmaceutical bulletin.