Nifedipine inhibits calcium-activated K transport in human erythrocytes.

The effect of nifedipine on K transport across human erythrocytes was investigated. Nifedipine had no effect on K influx mediated by the Na-K pump, Na-K-2Cl cotransport, or the passive residual K flux. However, it inhibited the K and water loss from ATP-depleted cells in the presence of external Ca (Cao). Similar inhibition of Ca-activated K [K(Ca)] efflux was observed in fresh cells exposed to Cao and A23187 or ionomycin. The inhibition was observed even when nifedipine was added after initiation of the K(Ca) efflux and was not readily reversed by washing cells with drug-free media. When K(Ca) efflux was plotted as a function of external free Ca, nifedipine reduced the maximum K(Ca) efflux but had no effect on the Ca concentration required for half-maximum K(Ca) efflux. The inhibition of K(Ca) efflux by nifedipine was not consequent to its effect on conductive Cl permeability, because valinomycin-induced K efflux in Cl media was enhanced rather than reduced by nifedipine and because the inhibition was also seen with SCN, a nonlimiting anion. Nifedipine inhibited the K(Ca) efflux with a dissociation constant (Kd) of 4 microM. The inhibitory capacity of nifedipine was reduced by increasing external K. Nifedipine reduced not only the basic conductance but also the zero-current K conductance with a Kd of 23 microM. Other Ca-channel blockers, such as verapamil and diltiazem, did not inhibit K(Ca) efflux, but other dihydropyridines, including BAY K 8644, a Ca-channel agonist, were effective in inhibiting K(Ca) efflux.(ABSTRACT TRUNCATED AT 250 WORDS)