Inhibition and activation of Na/sup +/-Ca/sup 2 +/ exchange activity by quinacrine

Journal Article · Thu Jan 01 04:00:00 EST 1987 · Am. J. Physiol.; (United States)

OSTI ID:6218846

de la Pena, P; Reeves, J P

Quinacrine either inhibited or stimulated Na-Ca exchange in cardiac sarcolemmal vesicles, depending on the experimental conditions. When present in the assay medium for Na-Ca exchange, quinacrine inhibited both Na/sub i/-dependent Ca/sup 2 +/ uptake (K/sub i/ = 50 ..mu..M) and Na/sub 0/-dependent Ca/sup 2 +/ efflux. Quinacrine's inhibition of Ca/sub 2//sup +/ efflux was attenuated by high concentrations of Na/sup +/. Quinacrine also blocked Na-Na and Ca-Ca exchange activities in the vesicles. The inhibitory effects of quinacrine on Na-Ca exchange activity are qualitatively similar to those reported previously for amiloride derivatives. When Na-loaded vesicles were preincubated with quinacrine and then assayed for Na-Ca exchange in a quinacrine-free medium, stimulation of exchange activity was observed. This stimulation was reversible on the removal of bound quinacrine and involved a reduction in the apparent K/sub m/ for extravesicular Ca/sup 2 +/. Stimulation of exchange activity under these conditions was also observed with the lipophilic cations tetraphenylphosphonium. Since Ca/sup 2 +/, quinacrine and tetraphenylphosphonium all bind strongly to sarcolemmal membranes it is suggested that the observed stimulation of exchange activity involves a local electrostatic effect of the bound cations in accelerating a rate-limiting step in the reaction mechanism for Na-Ca exchange.

• Research Organization: Roche Institute of Molecular Biology, Nutley, NJ
• OSTI ID: 6218846
• Journal Information: Am. J. Physiol.; (United States), Journal Name: Am. J. Physiol.; (United States) Vol. 252:1; ISSN AJPHA
• Country of Publication: United States
• Language: English

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