EFFECT OF QUINIDINE ON CATION-EXCHANGE IN CULTURED-CELLS

  • 1 January 1976
    • journal article
    • research article
    • Vol. 197  (3) , 605-614
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 s of application. Passive Na influx (pmol/cm2 per s) 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 resulted in a return of Na influx to control levels within 1-3 min. After 1-2 min of quinidine treatment, coupled active Na efflux/K influx rapidly declined, reaching minimum values for each concentration between 2-4 min 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 h. 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 min or less) both ions were in flux equilibrium, explaining the absence of change in [Nai] and [Ki] in the presence of quinidine. Calculations of ECl [Cl equilibrium potential] indicated that, when present for 4 h, quinidine did not change the Em [membrane potential] in these cells although significant (P < .001) reductions in apparent P[permeability]na and PK values were recorded. The effect on PNa was much greater than that on PK. The quinidine-induced flux changes occurred in a definite temporal sequence suggesting that they could all be explained on the basis of 1 direct initial action. This initial direct action, i.e., 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.