AJP - Cell Physiology, Vol 259, Issue 2 C332-C339, Copyright © 1990 by American Physiological Society
Nifedipine inhibits calcium-activated K transport in human erythrocytes
D. M. Kaji
Renal Section, Veterans Administration Medical Center, Bronx 10468.
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)
