AJP - Heart and Circulatory Physiology, Vol 272, Issue 6 2833-H2842, Copyright © 1997 by American Physiological Society

ARTICLES

Stage-dependent changes in membrane currents in rats with monocrotaline-induced right ventricular hypertrophy

J. K. Lee, I. Kodama, H. Honjo, T. Anno, K. Kamiya and J. Toyama
Department of Circulation, Nagoya University, Japan.

Sequential changes in action potential configuration, 4-amino-pyridine-sensitive transient outward current (Ito), and L-type calcium current (ICa) in association with hypertrophy were investigated in ventricular myocytes from rats with monocrotaline (MCT)-induced pulmonary hypertension. The tissue weight ratio of right ventricle (RV) to left ventricle plus septum 14 and 28 days after a subcutaneous injection of MCT increased by 29.7 and 77.2%, respectively. Action potential duration (APD) of RV cells from MCT rats increased progressively, prolonged by 73.2 and 92.2% on days 14 and 28, respectively. The current density of Ito in RV cells from MCT rats on day 14 (32.5 +/- 4.5 pA/pF, n = 13) was significantly larger than in controls (26.8 +/- 4.5 pA/pF, n = 8; P < 0.05). On day 28, however, Ito density in MCT rats (15.3 +/- 4.6 pA/pF, n = 9) was significantly less than in controls (27.3 +/- 4.2 pA/pF, n = 10; P < 0.05). There were no differences in the voltage dependence of steady-state activation and inactivation of Ito between MCT and control rats. ICa density in MCT rats on day 14 (15.7 +/- 2.6 pA/pF, n = 10) was significantly larger than in controls (10.0 +/- 2.3 pA/pF, n = 10; P < 0.05), but there was no significant difference in Ito density between MCT rats (8.3 +/- 3.7 pA/pF, n = 10) and controls (11.6 +/- 3.0 pA/pF, n = 10) on day 28. These findings suggest that hypertrophy of mammalian hearts may cause stage-dependent changes in Ito and ICa density of ventricular myocytes. The APD prolongation in the early stage of hypertrophy may be caused mainly by an increase in ICa density, whereas the APD prolongation in the late stage may be ascribed to a reduction in Ito density.

This article has been cited by other articles:

				J. P. Versluis, J. W. Heslinga, P. Sipkema, and N. Westerhof Contractile reserve but not tension is reduced in monocrotaline-induced right ventricular hypertrophy Am J Physiol Heart Circ Physiol, March 1, 2004; 286(3): H979 - H984. [Abstract] [Full Text] [PDF]

				R. Kaprielian, R. Sah, T. Nguyen, A. D. Wickenden, and P. H. Backx Myocardial infarction in rat eliminates regional heterogeneity of AP profiles, Ito K+ currents, and [Ca2+]i transients Am J Physiol Heart Circ Physiol, September 1, 2002; 283(3): H1157 - H1168. [Abstract] [Full Text] [PDF]

				L. Chen, X. T. Gan, J. V. Haist, Q. Feng, X. Lu, S. Chakrabarti, and M. Karmazyn Attenuation of Compensatory Right Ventricular Hypertrophy and Heart Failure following Monocrotaline-Induced Pulmonary Vascular Injury by the Na+-H+ Exchange Inhibitor Cariporide J. Pharmacol. Exp. Ther., August 1, 2001; 298(2): 469 - 476. [Abstract] [Full Text] [PDF]

				M. Uzzaman, H. Honjo, Y. Takagishi, L. Emdad, A. I. Magee, N. J. Severs, and I. Kodama Remodeling of Gap Junctional Coupling in Hypertrophied Right Ventricles of Rats With Monocrotaline-Induced Pulmonary Hypertension Circ. Res., April 28, 2000; 86(8): 871 - 878. [Abstract] [Full Text] [PDF]

				J.-K. Lee, A. Nishiyama, F. Kambe, H. Seo, S. Takeuchi, K. Kamiya, I. Kodama, and J. Toyama Downregulation of voltage-gated K+ channels in rat heart with right ventricular hypertrophy Am J Physiol Heart Circ Physiol, November 1, 1999; 277(5): H1725 - H1731. [Abstract] [Full Text] [PDF]