The action of Na+ as a cofactor in the inhibition by cytoplasmic protons of the cardiac Na(+)-Ca2+ exchanger in the guinea-pig - PubMed (original) (raw)
The action of Na+ as a cofactor in the inhibition by cytoplasmic protons of the cardiac Na(+)-Ca2+ exchanger in the guinea-pig
A E Doering et al. J Physiol. 1994.
Abstract
1. Na(+)-Ca2+ exchange current was activated in giant excised patches of guinea-pig cardiac sarcolemma by raising the intracellular sodium concentration ([Na+]i). When the pHi was simultaneously acidified to 6.4, the current was transient, dropping by 80% in 30 s. 2. Pre-exposure to a pHi of 6.4 for 15 s reduced the peak Na(+)-Ca2+ exchange current without altering the decay rate or steady-state current. Recovery from proton inhibition was seen when [Na+]i was removed for 9 s. 3. A mathematical model of Na(+)-Ca2+ exchange function reproduced the experimental results. In addition, two model-dependent predictions were seen experimentally. (i) [Na+]i-dependent 'inactivation' of Na(+)-Ca2+ exchange may arise from pHi effects. We observed experimentally that pre-exposure to acidic pHi can remove the transient current component attributed to [Na+]i-dependent 'inactivation'. (ii) self-exchange should be inhibited by acidification. This has been observed by other investigators. 4. We have hypothesized that there are two components to inhibition of the Na(+)-Ca2+ exchanger by intracellular protons, and that one is enhanced by increased [Na+]i (Doering & Lederer, 1993b). This hypothesis is supported by the data presented here and by a model of Na(+)-Ca2+ exchange behaviour in which binding of intracellular sodium to the exchanger enhances the affinity of the exchanger for inhibitory intracellular protons.
Similar articles
- The mechanism by which cytoplasmic protons inhibit the sodium-calcium exchanger in guinea-pig heart cells.
Doering AE, Lederer WJ. Doering AE, et al. J Physiol. 1993 Jul;466:481-99. J Physiol. 1993. PMID: 8410703 Free PMC article. - Inactivation of outward Na(+)-Ca2+ exchange current in guinea-pig ventricular myocytes.
Matsuoka S, Hilgemann DW. Matsuoka S, et al. J Physiol. 1994 May 1;476(3):443-58. doi: 10.1113/jphysiol.1994.sp020146. J Physiol. 1994. PMID: 7520059 Free PMC article. - Paradoxical block of the Na+-Ca2+ exchanger by extracellular protons in guinea-pig ventricular myocytes.
Egger M, Niggli E. Egger M, et al. J Physiol. 2000 Mar 1;523 Pt 2(Pt 2):353-66. doi: 10.1111/j.1469-7793.2000.t01-1-00353.x. J Physiol. 2000. PMID: 10699080 Free PMC article. - Molecular studies of the cardiac sarcolemmal sodium-calcium exchanger.
Nicoll DA, Philipson KD. Nicoll DA, et al. Ann N Y Acad Sci. 1991;639:181-8. doi: 10.1111/j.1749-6632.1991.tb17305.x. Ann N Y Acad Sci. 1991. PMID: 1785844 Review. - Effects of amiloride on the cardiovascular system: role of Na+/Ca2+ exchange.
Luciani S, Bova S, Cargnelli G, Debetto P. Luciani S, et al. Pharmacol Res. 1992 May-Jun;25(4):303-10. doi: 10.1016/1043-6618(92)90666-y. Pharmacol Res. 1992. PMID: 1409243 Review. No abstract available.
Cited by
- Cardiac function is regulated by the sodium-dependent inhibition of the sodium-calcium exchanger NCX1.
Scranton K, John S, Angelini M, Steccanella F, Umar S, Zhang R, Goldhaber JI, Olcese R, Ottolia M. Scranton K, et al. Nat Commun. 2024 May 7;15(1):3831. doi: 10.1038/s41467-024-47850-z. Nat Commun. 2024. PMID: 38714663 Free PMC article. - Skeletal and cardiac muscle calcium transport regulation in health and disease.
Valentim MA, Brahmbhatt AN, Tupling AR. Valentim MA, et al. Biosci Rep. 2022 Dec 22;42(12):BSR20211997. doi: 10.1042/BSR20211997. Biosci Rep. 2022. PMID: 36413081 Free PMC article. Review. - Modulation of the cardiac Na+-Ca2+ exchanger by cytoplasmic protons: Molecular mechanisms and physiological implications.
Scranton K, John S, Escobar A, Goldhaber JI, Ottolia M. Scranton K, et al. Cell Calcium. 2020 May;87:102140. doi: 10.1016/j.ceca.2019.102140. Epub 2019 Dec 11. Cell Calcium. 2020. PMID: 32070924 Free PMC article. Review. - Molecular determinants of pH regulation in the cardiac Na+-Ca2+ exchanger.
John S, Kim B, Olcese R, Goldhaber JI, Ottolia M. John S, et al. J Gen Physiol. 2018 Feb 5;150(2):245-257. doi: 10.1085/jgp.201611693. Epub 2018 Jan 4. J Gen Physiol. 2018. PMID: 29301861 Free PMC article. - Sodium-calcium exchangers (NCX): molecular hallmarks underlying the tissue-specific and systemic functions.
Khananshvili D. Khananshvili D. Pflugers Arch. 2014 Jan;466(1):43-60. doi: 10.1007/s00424-013-1405-y. Epub 2013 Nov 27. Pflugers Arch. 2014. PMID: 24281864 Review.
References
- Biochemistry. 1990 Mar 13;29(10):2437-42 - PubMed
- Science. 1990 Apr 20;248(4953):376-8 - PubMed
- Science. 1990 Oct 26;250(4980):562-5 - PubMed
- Nature. 1991 Feb 14;349(6310):621-4 - PubMed
- Nature. 1991 Aug 22;352(6337):715-8 - PubMed
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Miscellaneous