Depolarization-induced Ca entry via Na-Ca exchange triggers SR release in guinea pig cardiac myocytes - PubMed (original) (raw)
Depolarization-induced Ca entry via Na-Ca exchange triggers SR release in guinea pig cardiac myocytes
A J Levi et al. Am J Physiol. 1994 Apr.
Abstract
In mammalian heart muscle, Ca entry through L-type Ca channels is thought to be the primary trigger for the sarcoplasmic reticulum (SR) Ca release, which initiates contraction. The results of this study show that, in guinea pig myocytes with a normal internal Na (10 mM Na in pipette), another trigger mechanisms for SR release and contraction exists. A crucial feature of these experiments was the ability to change rapidly the extracellular environment of a single myocyte so that alterations of intracellular Ca and SR Ca load were minimized for each solution change. We found the following results. 1) A switch to Na-free solution 50 ms before depolarization led to an increase of phasic contraction without increasing L-type Ca current (Ica) or Ca loading of the SR. 2) Although rapid application of 20 microM nifedipine 3 s before a + 10-mV pulse blocked ICa completely, 43 +/- 11 (SE) % of the phasic contraction remained. Similar results were obtained by rapid switching to 150 microM Cd to block ICa. 3) Phasic contraction and ICa had different voltage dependence. With steps to positive potentials there was little ICa but still a substantial phasic contraction. 4) Under action potential conditions, 64.6 +/- 7.9% of the control phasic contraction remained after switching to 20 microM nifedipine to block ICa. 5) The contraction remaining with nifedipine was unaffected by adding 100 microM Ni. Because 100 microM Ni blocks T-type Ca channels, this shows that Ca entry via T-type Ca channels is not involved in triggering SR release. 6) The phasic contraction remaining after a rapid switch to nifedipine was blocked completely by adding 5 mM Ni. Because this concentration of Ni is known to block the Na-Ca exchange, this result suggests that the exchange plays a role in triggering SR release. Taken together, the present results indicate that depolarization-induced Ca entry on the Na-Ca exchange is able to trigger SR release and phasic contraction. This explanation can account for increased phasic contraction after a rapid switch to Na-free solution, persistence of a phasic contraction in the complete absence of ICa, substantial phasic contraction at positive test potentials where there is no ICa, and abolition of nifedipine-resistant contraction by 5 mM Ni.
Similar articles
- Voltage dependence of the Fura-2 transient in rabbit left atrial myocytes at 37 degrees C.
Mitcheson JS, Hancox JC, Levi AJ. Mitcheson JS, et al. Pflugers Arch. 1997 Apr;433(6):817-26. doi: 10.1007/s004240050350. Pflugers Arch. 1997. PMID: 9049175 - Effect on the fura-2 transient of rapidly blocking the Ca2+ channel in electrically stimulated rabbit heart cells.
Levi AJ, Issberner J. Levi AJ, et al. J Physiol. 1996 May 15;493 ( Pt 1)(Pt 1):19-37. doi: 10.1113/jphysiol.1996.sp021362. J Physiol. 1996. PMID: 8735692 Free PMC article. - Evidence that reverse Na-Ca exchange can trigger SR calcium release.
Litwin S, Kohmoto O, Levi AJ, Spitzer KW, Bridge JH. Litwin S, et al. Ann N Y Acad Sci. 1996 Apr 15;779:451-63. doi: 10.1111/j.1749-6632.1996.tb44820.x. Ann N Y Acad Sci. 1996. PMID: 8659861 Review. - One hump or two? The triggering of calcium release from the sarcoplasmic reticulum and the voltage dependence of contraction in mammalian cardiac muscle.
Levi AJ, Brooksby P, Hancox JC. Levi AJ, et al. Cardiovasc Res. 1993 Oct;27(10):1743-57. doi: 10.1093/cvr/27.10.1743. Cardiovasc Res. 1993. PMID: 8275519 Review.
Cited by
- Different Densities of Na-Ca Exchange Current in T-Tubular and Surface Membranes and Their Impact on Cellular Activity in a Model of Rat Ventricular Cardiomyocyte.
Pásek M, Šimurda J, Christé G. Pásek M, et al. Biomed Res Int. 2017;2017:6343821. doi: 10.1155/2017/6343821. Epub 2017 Feb 22. Biomed Res Int. 2017. PMID: 28321411 Free PMC article. - Na/Ca exchange and contraction of the heart.
Ottolia M, Torres N, Bridge JH, Philipson KD, Goldhaber JI. Ottolia M, et al. J Mol Cell Cardiol. 2013 Aug;61:28-33. doi: 10.1016/j.yjmcc.2013.06.001. Epub 2013 Jun 12. J Mol Cell Cardiol. 2013. PMID: 23770352 Free PMC article. Review. - Na+ currents are required for efficient excitation-contraction coupling in rabbit ventricular myocytes: a possible contribution of neuronal Na+ channels.
Torres NS, Larbig R, Rock A, Goldhaber JI, Bridge JH. Torres NS, et al. J Physiol. 2010 Nov 1;588(Pt 21):4249-60. doi: 10.1113/jphysiol.2010.194688. J Physiol. 2010. PMID: 20837647 Free PMC article. - Organization of ryanodine receptors, transverse tubules, and sodium-calcium exchanger in rat myocytes.
Jayasinghe I, Cannell MB, Soeller C. Jayasinghe I, et al. Biophys J. 2009 Nov 18;97(10):2664-73. doi: 10.1016/j.bpj.2009.08.036. Biophys J. 2009. PMID: 19917219 Free PMC article. - Accelerated inactivation of the L-type calcium current due to a mutation in CACNB2b underlies Brugada syndrome.
Cordeiro JM, Marieb M, Pfeiffer R, Calloe K, Burashnikov E, Antzelevitch C. Cordeiro JM, et al. J Mol Cell Cardiol. 2009 May;46(5):695-703. doi: 10.1016/j.yjmcc.2009.01.014. J Mol Cell Cardiol. 2009. PMID: 19358333 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous