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Titolo:
Changes in ryanodine receptor-mediated calcium release during skeletal muscle differentiation. II. Resolution of a caffeine-ryanodine paradox
Autore:
Wingertzahn, MA; Ochs, RS;
Indirizzi:
St Johns Univ, Dept Pharm & Allied Hlth, Jamaica, NY 11439 USA St Johns Univ Jamaica NY USA 11439 m & Allied Hlth, Jamaica, NY 11439 USA
Titolo Testata:
EXPERIMENTAL BIOLOGY AND MEDICINE
fascicolo: 2, volume: 226, anno: 2001,
pagine: 119 - 126
SICI:
1535-3702(200102)226:2<119:CIRRCR>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
CAPACITATIVE CA2+ ENTRY; SARCOPLASMIC-RETICULUM; DIHYDROPYRIDINE RECEPTOR; INTRALUMINAL CA2+; CELLS; CHANNEL; STORES; ANTAGONISTS; EXPRESSION; PROTEINS;
Keywords:
ryanodine; ryanodine receptor; calcium release; caffeine;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
32
Recensione:
Indirizzi per estratti:
Indirizzo: Ochs, RS St Johns Univ, Dept Pharm & Allied Hlth, Jamaica, NY 11439 USA StJohns Univ Jamaica NY USA 11439 d Hlth, Jamaica, NY 11439 USA
Citazione:
M.A. Wingertzahn e R.S. Ochs, "Changes in ryanodine receptor-mediated calcium release during skeletal muscle differentiation. II. Resolution of a caffeine-ryanodine paradox", EXP BIOL ME, 226(2), 2001, pp. 119-126

Abstract

Our previous study demonstrated a disparity of action between two established pharmacological modulators of the same calcium (Ca2+) release channel, the ryanodine receptor (RyR). Specifically, we observed that caffeine sensitivity was elicited at earlier stages of development than that of ryanodine. In the present study, we offer a hypothesis to resolve this paradox. We provide evidence that ryanodine acts as a pure uncompetitive inhibitor of Ca2+ transport, with respect to Ca2+ itself, This explains why little ryanodine inhibition was observed at low Ca2+ concentrations, while maximal ryanodine inhibition was observed at saturating Ca2+ concentrations. In order to exclude the possibility of nonspecific ryanodine actions as an alternative explanation, we established the phenomenon of capacitative calcium entry (CCE) for L6 cells, Since it is known that CCE is inversely correlated with [Ca2+] of the ER/SR lumen, the extent of CCE is therefore an indirect measure of Ca2+ concentration within the SR. We also demonstrated the functional pathway for Ca2+ entry. Employing pharmacological inhibitors, we found thata T-type plasma membrane channel was predominant in the myoblasts, while an L-type channel was predominant in the adult myotubes. Our data using these inhibitors made nonspecific ryanodine actions an unlikely explanation of the disparity in action between ryanodine and caffeine. Moreover, we found no evidence that inositol trisphosphate, a proposed regulator of CCE for other cells, could influence CCE in L6 cells. We conclude that the disparity between caffeine and ryanodine can be explained by Ca2+ dependence of ryanodine action. This study may also offer an explanation of other studies showing unclear actions of ryanodine binding and action.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/04/20 alle ore 12:51:02