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Investigation of the mechanisms underlying the increased contraction of hypertrophied ventricular myocytes isolated from the spontaneously hypertensive rat.
Cardiovasc Res. 1993 Jul; 27(7):1268-77.CR

Abstract

OBJECTIVE

The aim was to investigate the cellular mechanisms responsible for the increased contraction of left ventricular myocytes isolated from the spontaneously hypertensive rat (SHR).

METHODS

Single myocytes were isolated enzymatically from the left ventricles of SHR, Wistar-Kyoto (WKY), and Wistar rats. WKY and Wistar myocytes were used as normotensive controls. Cytoplasmic calcium was measured with Fura-2 and contraction was measured optically. Membrane potential was measured with microelectrodes and cells were voltage clamped to measure the amplitude of L-type calcium current (iCa).

RESULTS

Under action potential conditions, SHR myocytes had a larger calcium transient and an increased sarcoplasmic reticular calcium content compared to normotensive myocytes. There was no detectable difference in the resting cytoplasmic calcium concentration between SHR and control myocytes. SHR myocytes also had a prolonged action potential compared to normotensive cells. However, when cells were voltage clamped and short pulses of 120 ms duration were applied (a similar duration of depolarisation to the action potential), the difference in the calcium transient or contraction between SHR and normotensive myocytes was abolished. SHR myocytes had an unchanged amplitude of ICa in comparison to control myocytes, and there was no detectable difference in the myofilament response to calcium between SHR and control myocytes.

CONCLUSIONS

(1) Hypertrophied SHR myocytes stimulated with action potentials had an increased calcium transient compared to normotensive cells. The greater calcium transient in the SHR cells is likely to be a major factor responsible for their increased contraction. (2) SHR myocytes had a prolonged action potential in comparison to normotensive cells. (3) The amplitude of ICa and myofilament response to calcium were unchanged in SHR myocytes, suggesting that these factors do not play a role in the increased contraction of these cells. (4) Since the difference between SHR and control cells was abolished by voltage clamping the cells to prevent the difference of action potential, it is unlikely that an alteration of intrinsic mechanisms in SHR myocytes is responsible for their increased contraction. Rather, it suggests that the prolonged action potential of SHR myocytes plays a important role in causing their increased calcium transient and contraction. Our results indicate that the prolonged action potential in SHR cells results in an increased calcium content of the sarcoplasmic reticulum, which leads to a greater sarcoplasmic reticular calcium release upon stimulation and an increased contraction.

Authors+Show Affiliations

Department of Physiology, School of Medical Sciences, University of Bristol, University Walk, United Kingdom.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

8252588

Citation

Brooksby, P, et al. "Investigation of the Mechanisms Underlying the Increased Contraction of Hypertrophied Ventricular Myocytes Isolated From the Spontaneously Hypertensive Rat." Cardiovascular Research, vol. 27, no. 7, 1993, pp. 1268-77.
Brooksby P, Levi AJ, Jones JV. Investigation of the mechanisms underlying the increased contraction of hypertrophied ventricular myocytes isolated from the spontaneously hypertensive rat. Cardiovasc Res. 1993;27(7):1268-77.
Brooksby, P., Levi, A. J., & Jones, J. V. (1993). Investigation of the mechanisms underlying the increased contraction of hypertrophied ventricular myocytes isolated from the spontaneously hypertensive rat. Cardiovascular Research, 27(7), 1268-77.
Brooksby P, Levi AJ, Jones JV. Investigation of the Mechanisms Underlying the Increased Contraction of Hypertrophied Ventricular Myocytes Isolated From the Spontaneously Hypertensive Rat. Cardiovasc Res. 1993;27(7):1268-77. PubMed PMID: 8252588.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Investigation of the mechanisms underlying the increased contraction of hypertrophied ventricular myocytes isolated from the spontaneously hypertensive rat. AU - Brooksby,P, AU - Levi,A J, AU - Jones,J V, PY - 1993/7/1/pubmed PY - 1993/7/1/medline PY - 1993/7/1/entrez SP - 1268 EP - 77 JF - Cardiovascular research JO - Cardiovasc Res VL - 27 IS - 7 N2 - OBJECTIVE: The aim was to investigate the cellular mechanisms responsible for the increased contraction of left ventricular myocytes isolated from the spontaneously hypertensive rat (SHR). METHODS: Single myocytes were isolated enzymatically from the left ventricles of SHR, Wistar-Kyoto (WKY), and Wistar rats. WKY and Wistar myocytes were used as normotensive controls. Cytoplasmic calcium was measured with Fura-2 and contraction was measured optically. Membrane potential was measured with microelectrodes and cells were voltage clamped to measure the amplitude of L-type calcium current (iCa). RESULTS: Under action potential conditions, SHR myocytes had a larger calcium transient and an increased sarcoplasmic reticular calcium content compared to normotensive myocytes. There was no detectable difference in the resting cytoplasmic calcium concentration between SHR and control myocytes. SHR myocytes also had a prolonged action potential compared to normotensive cells. However, when cells were voltage clamped and short pulses of 120 ms duration were applied (a similar duration of depolarisation to the action potential), the difference in the calcium transient or contraction between SHR and normotensive myocytes was abolished. SHR myocytes had an unchanged amplitude of ICa in comparison to control myocytes, and there was no detectable difference in the myofilament response to calcium between SHR and control myocytes. CONCLUSIONS: (1) Hypertrophied SHR myocytes stimulated with action potentials had an increased calcium transient compared to normotensive cells. The greater calcium transient in the SHR cells is likely to be a major factor responsible for their increased contraction. (2) SHR myocytes had a prolonged action potential in comparison to normotensive cells. (3) The amplitude of ICa and myofilament response to calcium were unchanged in SHR myocytes, suggesting that these factors do not play a role in the increased contraction of these cells. (4) Since the difference between SHR and control cells was abolished by voltage clamping the cells to prevent the difference of action potential, it is unlikely that an alteration of intrinsic mechanisms in SHR myocytes is responsible for their increased contraction. Rather, it suggests that the prolonged action potential of SHR myocytes plays a important role in causing their increased calcium transient and contraction. Our results indicate that the prolonged action potential in SHR cells results in an increased calcium content of the sarcoplasmic reticulum, which leads to a greater sarcoplasmic reticular calcium release upon stimulation and an increased contraction. SN - 0008-6363 UR - https://www.unboundmedicine.com/medline/citation/8252588/Investigation_of_the_mechanisms_underlying_the_increased_contraction_of_hypertrophied_ventricular_myocytes_isolated_from_the_spontaneously_hypertensive_rat_ L2 - https://academic.oup.com/cardiovascres/article-lookup/doi/10.1093/cvr/27.7.1268 DB - PRIME DP - Unbound Medicine ER -