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The electrophysiological characteristics of hypertrophied ventricular myocytes from the spontaneously hypertensive rat.
J Hypertens. 1993 Jun; 11(6):611-22.JH

Abstract

OBJECTIVE

Previous studies on multicellular preparations have shown that hypertrophied cardiac muscle from the spontaneously hypertensive rat (SHR) has a prolonged action potential. The first aim of the present study was to determine whether the action potential of isolated left ventricular myocytes was similarly prolonged and to study the underlying membrane currents that might be responsible. The second aim was to evaluate the L-type calcium current amplitude of SHR myocytes, as we have recently shown that they have an increased contraction and an increase in the calcium trigger entering via the L-type calcium channel might be one possible mechanism for this.

METHODS

The electrophysiological characteristics of left ventricular myocytes isolated from the SHR were compared with those from normotensive control rats. Action potentials were recorded with microelectrodes. Cells were voltage-clamped and the membrane currents elicited by steps to different potentials were analysed. Blockers of potassium and calcium currents were used to reveal the contribution made by these currents to net membrane currents.

RESULTS

SHR myocytes had prolonged action potentials. The action potential duration of SHR myocytes at 90% repolarization was found to be longer, although at 20% and 50% repolarization no difference was found. There was no difference in the resting membrane potential between SHR and control myocytes. Using a voltage clamp we studied the L-type calcium current and potassium currents. The major change in SHR myocytes was a decrease in the magnitude (normalized to the membrane capacitance) of the inward rectifier potassium current elicited by negative potentials. There was no detectable difference in either the transient outward or delayed rectifier potassium currents. We also found no difference in the magnitude, time course or voltage dependence of L-type calcium current in hypertrophied SHR myocytes.

CONCLUSIONS

First, the action potential of SHR myocytes was prolonged compared with control myocytes. Secondly, the main change in SHR myocytes was that pulses to negative potentials elicited a lower inward rectifier potassium current. A reduction in the density of inward rectifier channels might play a role in prolonging the SHR action potential, since a lower outward repolarizing current will flow through inward rectifier potassium channels during the SHR action potential repolarization. Thirdly, there was no difference in L-type calcium current density or time course between SHR and control myocytes. Thus, a change in L-type calcium current probably plays no role in causing the prolonged SHR action potential or the increased contraction of hypertrophied SHR ventricular myocytes. Finally, the prolonged action potential in SHR myocytes may itself be one factor responsible for the increased contraction of these cells.

Authors+Show Affiliations

Department of Physiology, School of Medical Sciences, University of Bristol, UK.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

8397240

Citation

Brooksby, P, et al. "The Electrophysiological Characteristics of Hypertrophied Ventricular Myocytes From the Spontaneously Hypertensive Rat." Journal of Hypertension, vol. 11, no. 6, 1993, pp. 611-22.
Brooksby P, Levi AJ, Jones JV. The electrophysiological characteristics of hypertrophied ventricular myocytes from the spontaneously hypertensive rat. J Hypertens. 1993;11(6):611-22.
Brooksby, P., Levi, A. J., & Jones, J. V. (1993). The electrophysiological characteristics of hypertrophied ventricular myocytes from the spontaneously hypertensive rat. Journal of Hypertension, 11(6), 611-22.
Brooksby P, Levi AJ, Jones JV. The Electrophysiological Characteristics of Hypertrophied Ventricular Myocytes From the Spontaneously Hypertensive Rat. J Hypertens. 1993;11(6):611-22. PubMed PMID: 8397240.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The electrophysiological characteristics of hypertrophied ventricular myocytes from the spontaneously hypertensive rat. AU - Brooksby,P, AU - Levi,A J, AU - Jones,J V, PY - 1993/6/1/pubmed PY - 1993/6/1/medline PY - 1993/6/1/entrez SP - 611 EP - 22 JF - Journal of hypertension JO - J Hypertens VL - 11 IS - 6 N2 - OBJECTIVE: Previous studies on multicellular preparations have shown that hypertrophied cardiac muscle from the spontaneously hypertensive rat (SHR) has a prolonged action potential. The first aim of the present study was to determine whether the action potential of isolated left ventricular myocytes was similarly prolonged and to study the underlying membrane currents that might be responsible. The second aim was to evaluate the L-type calcium current amplitude of SHR myocytes, as we have recently shown that they have an increased contraction and an increase in the calcium trigger entering via the L-type calcium channel might be one possible mechanism for this. METHODS: The electrophysiological characteristics of left ventricular myocytes isolated from the SHR were compared with those from normotensive control rats. Action potentials were recorded with microelectrodes. Cells were voltage-clamped and the membrane currents elicited by steps to different potentials were analysed. Blockers of potassium and calcium currents were used to reveal the contribution made by these currents to net membrane currents. RESULTS: SHR myocytes had prolonged action potentials. The action potential duration of SHR myocytes at 90% repolarization was found to be longer, although at 20% and 50% repolarization no difference was found. There was no difference in the resting membrane potential between SHR and control myocytes. Using a voltage clamp we studied the L-type calcium current and potassium currents. The major change in SHR myocytes was a decrease in the magnitude (normalized to the membrane capacitance) of the inward rectifier potassium current elicited by negative potentials. There was no detectable difference in either the transient outward or delayed rectifier potassium currents. We also found no difference in the magnitude, time course or voltage dependence of L-type calcium current in hypertrophied SHR myocytes. CONCLUSIONS: First, the action potential of SHR myocytes was prolonged compared with control myocytes. Secondly, the main change in SHR myocytes was that pulses to negative potentials elicited a lower inward rectifier potassium current. A reduction in the density of inward rectifier channels might play a role in prolonging the SHR action potential, since a lower outward repolarizing current will flow through inward rectifier potassium channels during the SHR action potential repolarization. Thirdly, there was no difference in L-type calcium current density or time course between SHR and control myocytes. Thus, a change in L-type calcium current probably plays no role in causing the prolonged SHR action potential or the increased contraction of hypertrophied SHR ventricular myocytes. Finally, the prolonged action potential in SHR myocytes may itself be one factor responsible for the increased contraction of these cells. SN - 0263-6352 UR - https://www.unboundmedicine.com/medline/citation/8397240/The_electrophysiological_characteristics_of_hypertrophied_ventricular_myocytes_from_the_spontaneously_hypertensive_rat_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=8397240.ui DB - PRIME DP - Unbound Medicine ER -