To understand the mechanism(s) underlying the Cd2+- and Co2+-induced increa
ses in the cytosolic free Ca2+ concentration ([Ca](i)) in cat adrenal chrom
affin cells, we used nystatin-perforated patch recording method and fura-2
microfluorometry. Under the current-clamp conditions, the external applicat
ion of 5 x 10(-7) M Cd2+ slowly depolarized the cells resulting in the burs
ting of action potentials. Under the voltage-clamp conditions, Cd2+ evoked
a slow inward current accompanied by a decrease of K+ conductance at a hold
ing potential of -40 mV, and Co2+ mimicked Cd2+ action. In some cells (16%)
, Cd2+ evoked an additional rapid transient outward current associated with
an increased K+ conductance and a successive slow inward current. The Cd2-induced inward current was activated in a concentration-dependent manner w
ith a half-maximum concentration of 9.3 X 10(-8) M. The Cd2+- and Co2+-indu
ced [Ca](i) increases measured with fura-2 microfluorometry were maximal at
10(-6) and 10(-5) M, respectively, and the higher concentrations of both c
ations caused the smaller responses. Additional transient increase in [Ca](
i) was often evoked upon the removal of relatively higher concentrations of
these metals. It was concluded that the Cd2+-induced membrane depolarizati
on due to the decrease in K+ conductances evoked the bursting firings resul
ting in the increase in [Ca](i), and consequently might stimulate the catec
holamine secretion. (C) 1999 Elsevier Science B.V. All rights reserved.