H+-activated Na+ influx in the ventricular myocyte couples Ca2+-signalling to intracellular pH
Acid extrusion on Na+-coupled pH-regulatory proteins (pH-transporters), Na+/H+ exchange (NHE1) and Na+-HCO3- co-transport (NBC), drives Na+ influx into the ventricular myocyte. This H+-activated Na+-influx is acutely up-regulated at pHi<7.2, greatly exceeding Na+-efflux on the Na+/K+ ATPase....
| Main Authors: | , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2013
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| _version_ | 1797073540267114496 |
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| author | Garciarena, C Youm, J Swietach, P Vaughan-Jones, R |
| author_facet | Garciarena, C Youm, J Swietach, P Vaughan-Jones, R |
| author_sort | Garciarena, C |
| collection | OXFORD |
| description | Acid extrusion on Na+-coupled pH-regulatory proteins (pH-transporters), Na+/H+ exchange (NHE1) and Na+-HCO3- co-transport (NBC), drives Na+ influx into the ventricular myocyte. This H+-activated Na+-influx is acutely up-regulated at pHi<7.2, greatly exceeding Na+-efflux on the Na+/K+ ATPase. It is spatially heterogeneous, due to the co-localisation of NHE1 protein (the dominant pH-transporter) with gap-junctions at intercalated discs. Overall Na+-influx via NBC is considerably lower, but much is co-localised with L-type Ca2+-channels in transverse-tubules. Through a functional coupling with Na+/Ca2+ exchange (NCX), H+-activated Na+-influx increases sarcoplasmic-reticular Ca2+-loading and release during intracellular acidosis. This raises Ca2+-transient amplitude, rescuing it from direct H+-inhibition. Functional coupling is biochemically regulated and linked to membrane receptors, through effects on NHE1 and NBC. It requires adequate cytoplasmic Na+-mobility, as NHE1 and NCX are spatially separated (up to 60μm). The relevant functional NCX activity must be close to dyads, as it exerts no effect on bulk diastolic Ca2+. H+-activated Na+-influx is up-regulated during ischaemia-reperfusion and some forms of maladaptive hypertrophy and heart failure. It is thus an attractive system for therapeutic manipulation. This article is part of a Special Issue entitled "Na+ Regulation in Cardiac Myocytes". © 2013 Elsevier Ltd. |
| first_indexed | 2024-03-06T23:23:37Z |
| format | Journal article |
| id | oxford-uuid:69a022d4-3727-4284-bb77-b1c5be6d4cf6 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:23:37Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | oxford-uuid:69a022d4-3727-4284-bb77-b1c5be6d4cf62022-03-26T18:52:14ZH+-activated Na+ influx in the ventricular myocyte couples Ca2+-signalling to intracellular pHJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:69a022d4-3727-4284-bb77-b1c5be6d4cf6EnglishSymplectic Elements at Oxford2013Garciarena, CYoum, JSwietach, PVaughan-Jones, RAcid extrusion on Na+-coupled pH-regulatory proteins (pH-transporters), Na+/H+ exchange (NHE1) and Na+-HCO3- co-transport (NBC), drives Na+ influx into the ventricular myocyte. This H+-activated Na+-influx is acutely up-regulated at pHi<7.2, greatly exceeding Na+-efflux on the Na+/K+ ATPase. It is spatially heterogeneous, due to the co-localisation of NHE1 protein (the dominant pH-transporter) with gap-junctions at intercalated discs. Overall Na+-influx via NBC is considerably lower, but much is co-localised with L-type Ca2+-channels in transverse-tubules. Through a functional coupling with Na+/Ca2+ exchange (NCX), H+-activated Na+-influx increases sarcoplasmic-reticular Ca2+-loading and release during intracellular acidosis. This raises Ca2+-transient amplitude, rescuing it from direct H+-inhibition. Functional coupling is biochemically regulated and linked to membrane receptors, through effects on NHE1 and NBC. It requires adequate cytoplasmic Na+-mobility, as NHE1 and NCX are spatially separated (up to 60μm). The relevant functional NCX activity must be close to dyads, as it exerts no effect on bulk diastolic Ca2+. H+-activated Na+-influx is up-regulated during ischaemia-reperfusion and some forms of maladaptive hypertrophy and heart failure. It is thus an attractive system for therapeutic manipulation. This article is part of a Special Issue entitled "Na+ Regulation in Cardiac Myocytes". © 2013 Elsevier Ltd. |
| spellingShingle | Garciarena, C Youm, J Swietach, P Vaughan-Jones, R H+-activated Na+ influx in the ventricular myocyte couples Ca2+-signalling to intracellular pH |
| title | H+-activated Na+ influx in the ventricular myocyte couples Ca2+-signalling to intracellular pH |
| title_full | H+-activated Na+ influx in the ventricular myocyte couples Ca2+-signalling to intracellular pH |
| title_fullStr | H+-activated Na+ influx in the ventricular myocyte couples Ca2+-signalling to intracellular pH |
| title_full_unstemmed | H+-activated Na+ influx in the ventricular myocyte couples Ca2+-signalling to intracellular pH |
| title_short | H+-activated Na+ influx in the ventricular myocyte couples Ca2+-signalling to intracellular pH |
| title_sort | h activated na influx in the ventricular myocyte couples ca2 signalling to intracellular ph |
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