Effect of quinidine on cation exchange in cultured cells

D. McCall

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

The effects of quinidine on membrane ion exchange were examined using monolayer cultures of mammalian cells. Quinidine, in concentrations from 10-6 to 10-3 M, produced a prompt inhibition of the passive Na influx, dose dependent along a sigmoid log dose response curve. This effect was at a maximum for each concentration of the drug within 30 seconds of application. Passive Na influx (pmol/cm2/sec) decreased from 18.8 to 17.6 (P < .05) and 10.5 (P < .001) in the presence of 10-6 and 10-3 M quinidine, respectively. In the continued presence of quinidine, there was no further time dependent effect on the Na influx, nor was there any tendency for the influx to recover. Washing the cells free of quinidine, however, resulted in a return of Na influx to control levels within 1 to 3 minutes. After 1 to 2 minute of quinidine treatment, coupled active Na efflux/K influx rapidly declined, reaching minimum values for each concentration between 2 to 4 minutes of drug treatment. Beyond that time, active Na/K fluxes again increased, but to values which remained significantly less than control, for up to 4 hours. Ten minutes of exposure to quinidine were required before any demonstrable effect on the passive K efflux could be recorded. In the presence of quinidine, there was reduced membrane turnover of both Na and K, but such that after a brief initial period (10 minutes or less) both ions were in flux equilibrium, explaining the absence of change in [Na(i)] and [K(i)] in the presence of quinidine. Calculations of E(Cl) indicated that, when present for 4 hours, quinidine did not change the E(m) in these cells although significant (P < .001) reductions in apparent P(Na) and P(K) values were recorded. The effect on P(Na) was much greater than that on P(K). The quinidine induced flux changes occurred in a definite temporal sequence suggesting that they could all be explained on the basis of one direct initial action. This initial direct action, namely the prompt reduction in Na influx, by modifying Na pump activity, could lead to a decreased K efflux, secondary to the depressed Na coupled active K influx via the Na pump.

Original languageEnglish (US)
Pages (from-to)605-614
Number of pages10
JournalJournal of Pharmacology and Experimental Therapeutics
Volume197
Issue number3
StatePublished - Dec 1 1976

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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