Steady-state coupling of plasma membrane calcium entry to extrusion revealed by novel L-type calcium channel block.
Cell Calcium
; 44(4): 353-62, 2008 Oct.
Article
em En
| MEDLINE
| ID: mdl-19230140
ABSTRACT
The L-type Ca2+ channel (Ca(v)1.2) is the main pathway for trans-sarcolemmal (SL) Ca2+ influx in cardiac myocytes. To maintain Ca2+ homeostasis, chronic SL Ca(2+)-influx must be matched by chronic SL efflux. In this study we tested the hypothesis that chronic downregulation of SL Ca2+ entry regulates SL extrusion. We studied mRNA and Ca2+ handling responses to chronic down-regulation of Ca2+ channel current induced by over-expression of the small GTPase Rem. Rem lowered net SL diastolic Ca2+ entry, and reduced the twitch Ca2+ amplitude. Rem also significantly slowed Ca2+ transient decay kinetics (p < 10(-3)). Rem reduced NCX1.1 protein level and function. To measure Na-Ca2+ exchange (NCX) function and sarcoplasmic reticulum (SR) store load we perfused Ca(2+)-free bath for 25s followed by rapid application of 50 mM caffeine. In control, caffeine transient relaxations were described by a bi-exponential decay with a fast phase that was 10 mM Ni(2+)-sensitive. Rem significantly slowed caffeine-induced relaxation time course (Rem versus control, p < 10(-6)). To test whether extrusion slowing was mediated by insufficient basal Ca2+ for allosteric NCX activation we measured the effect of increasing bath Ca2+ from 1.8 to 6 mM on caffeine-induced relaxation kinetics. 6 mM Ca2+ did not alter kinetics of control cells, but in Rem-over-expressed cells 6 mM Ca2+ sped kinetics. We conclude that chronic block of Ca(v)1.2 channel-mediated SL entry alters NCX expression, and coincidentally controls SR Ca loading and SL Ca2+ efflux.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sarcolema
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Cálcio
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Trocador de Sódio e Cálcio
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Proteínas Monoméricas de Ligação ao GTP
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Canais de Cálcio Tipo L
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Miócitos Cardíacos
Limite:
Animals
Idioma:
En
Revista:
Cell Calcium
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos