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A role for depolarisation induced calcium entry on the Na-Ca exchange in triggering intracellular calcium release and contraction in rat ventricular myocytes.
Cardiovasc Res. 1993 Sep; 27(9):1677-90.CR

Abstract

OBJECTIVE

The aim was to test whether depolarisation-induced calcium entry on the Na-Ca exchange is able to trigger calcium release from the sarcoplasmic reticulum in rat ventricular myocytes.

METHODS

Myocytes were isolated enzymatically from the left ventricle of the rat heart. Cells were impaled with narrow tipped microelectrodes to minimise intracellular dialysis and maintain normal internal ionic conditions. Cells were voltage clamped, contraction was measured optically, and in some experiments intracellular calcium was measured with Fura-2.

RESULTS

When the fast Na current was inactivated by using a holding potential of -40 mV, Ca entry via L-type Ca channels was expected to be the only mechanism capable of triggering sarcoplasmic reticular Ca release. In this situation, blocking L-type Ca channels should have abolished sarcoplasmic reticular release and the phasic twitch. However, after 2 min exposure to 20 microM nifedipine, which abolished the Ca current (ICa) completely, voltage clamp depolarisation from -40 mV to 0 mV still elicited 41(SEM 8.9)% of the control phasic twitch (n = 22 cells). This shows that there must be another mechanism, besides Ca entry via Ca channels, by which membrane depolarisation can trigger sarcoplasmic reticular release and the phasic twitch. The phasic twitch that remained in the presence of nifedipine increased progressively with the magnitude of step depolarisation, required a functional sarcoplasmic reticulum, was abolished by 5 mM external nickel, and was sensitive to both the Na and Ca transmembrane gradients.

CONCLUSIONS

The voltage dependent sarcolemmal Na-Ca exchange is predicted theoretically to generate a transient Ca entry at the start of a step membrane depolarisation, when membrane potential suddenly becomes more positive than the reversal potential of the Na-Ca exchange. The results of this study indicate that in rat myocytes with normal internal ions, physiological levels of membrane depolarisation generate a sufficient Ca entry on the exchange to trigger sarcoplasmic reticular calcium release and contraction. In the absence of ICa, this mechanism is capable of triggering a calcium release which leads to about 40% of the phasic contraction in cells depolarised from -40 mV to 0 mV. The existence of this sarcoplasmic triggering mechanism may have significance for the normal control of cardiac muscle contraction.

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Authors+Show Affiliations

Levi AJ
Department of Physiology, School of Medical Sciences, University of Bristol, United Kingdom.
Brooksby P
No affiliation info available
Hancox JC
No affiliation info available

MeSH

AnimalsCalciumCells, CulturedIon PumpsMembrane PotentialsMyocardial ContractionMyocardiumNifedipineRatsSarcoplasmic ReticulumSodium

Pub Type(s)

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

Language

eng

PubMed ID

8287448

Citation

Levi, A J., et al. "A Role for Depolarisation Induced Calcium Entry On the Na-Ca Exchange in Triggering Intracellular Calcium Release and Contraction in Rat Ventricular Myocytes." Cardiovascular Research, vol. 27, no. 9, 1993, pp. 1677-90.
Levi AJ, Brooksby P, Hancox JC. A role for depolarisation induced calcium entry on the Na-Ca exchange in triggering intracellular calcium release and contraction in rat ventricular myocytes. Cardiovasc Res. 1993;27(9):1677-90.
Levi, A. J., Brooksby, P., & Hancox, J. C. (1993). A role for depolarisation induced calcium entry on the Na-Ca exchange in triggering intracellular calcium release and contraction in rat ventricular myocytes. Cardiovascular Research, 27(9), 1677-90.
Levi AJ, Brooksby P, Hancox JC. A Role for Depolarisation Induced Calcium Entry On the Na-Ca Exchange in Triggering Intracellular Calcium Release and Contraction in Rat Ventricular Myocytes. Cardiovasc Res. 1993;27(9):1677-90. PubMed PMID: 8287448.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A role for depolarisation induced calcium entry on the Na-Ca exchange in triggering intracellular calcium release and contraction in rat ventricular myocytes. AU - Levi,A J, AU - Brooksby,P, AU - Hancox,J C, PY - 1993/9/1/pubmed PY - 1993/9/1/medline PY - 1993/9/1/entrez SP - 1677 EP - 90 JF - Cardiovascular research JO - Cardiovasc Res VL - 27 IS - 9 N2 - OBJECTIVE: The aim was to test whether depolarisation-induced calcium entry on the Na-Ca exchange is able to trigger calcium release from the sarcoplasmic reticulum in rat ventricular myocytes. METHODS: Myocytes were isolated enzymatically from the left ventricle of the rat heart. Cells were impaled with narrow tipped microelectrodes to minimise intracellular dialysis and maintain normal internal ionic conditions. Cells were voltage clamped, contraction was measured optically, and in some experiments intracellular calcium was measured with Fura-2. RESULTS: When the fast Na current was inactivated by using a holding potential of -40 mV, Ca entry via L-type Ca channels was expected to be the only mechanism capable of triggering sarcoplasmic reticular Ca release. In this situation, blocking L-type Ca channels should have abolished sarcoplasmic reticular release and the phasic twitch. However, after 2 min exposure to 20 microM nifedipine, which abolished the Ca current (ICa) completely, voltage clamp depolarisation from -40 mV to 0 mV still elicited 41(SEM 8.9)% of the control phasic twitch (n = 22 cells). This shows that there must be another mechanism, besides Ca entry via Ca channels, by which membrane depolarisation can trigger sarcoplasmic reticular release and the phasic twitch. The phasic twitch that remained in the presence of nifedipine increased progressively with the magnitude of step depolarisation, required a functional sarcoplasmic reticulum, was abolished by 5 mM external nickel, and was sensitive to both the Na and Ca transmembrane gradients. CONCLUSIONS: The voltage dependent sarcolemmal Na-Ca exchange is predicted theoretically to generate a transient Ca entry at the start of a step membrane depolarisation, when membrane potential suddenly becomes more positive than the reversal potential of the Na-Ca exchange. The results of this study indicate that in rat myocytes with normal internal ions, physiological levels of membrane depolarisation generate a sufficient Ca entry on the exchange to trigger sarcoplasmic reticular calcium release and contraction. In the absence of ICa, this mechanism is capable of triggering a calcium release which leads to about 40% of the phasic contraction in cells depolarised from -40 mV to 0 mV. The existence of this sarcoplasmic triggering mechanism may have significance for the normal control of cardiac muscle contraction. SN - 0008-6363 UR - https://www.unboundmedicine.com/medline/citation/8287448/A_role_for_depolarisation_induced_calcium_entry_on_the_Na_Ca_exchange_in_triggering_intracellular_calcium_release_and_contraction_in_rat_ventricular_myocytes_ L2 - https://academic.oup.com/cardiovascres/article-lookup/doi/10.1093/cvr/27.9.1677 DB - PRIME DP - Unbound Medicine ER -