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Effects of K⁺ Channel Blockers on K⁺ Channels, Membrane Potential, and Aldosterone Secretion in Rat Adrenal Zona Glomerulosa Cells¹

Department of Biological Sciences, Northern Illinois University, DeKalb, Illinois 60115

Address all correspondence and requests for reprints to: Dr. David P. Lotshaw, Department of Biological Sciences, Northern Illinois University, DeKalb, Illinois 60112.

The hypothesis that angiotensin II (ANG II)-induced aldosterone secretion is mediated through inhibition of plasma membrane K⁺ channels was examined by measuring the effects of K⁺ channel blockers on K⁺ currents, membrane potential, and aldosterone secretion in rat adrenal glomerulosa cells. Effective K⁺ channel blockers were identified and studied using patch clamp methods on isolated glomerulosa cells in cell culture. Extracellular Cs⁺ (2–20 mM) caused a voltage-dependent inhibition of macroscopic K⁺ currents, exhibiting an apparent K_d of 2 mM for blockade of K⁺ current at membrane potentials near the K⁺ equilibrium potential. Outward K⁺ current opposed the Cs⁺ block, imparting a steep voltage dependence to this block. In single channel studies Cs⁺ blocked inward, but not outward, unitary currents through ANG II-regulated weakly voltage-dependent K⁺ channels, which are thought to control resting membrane potential. Cs⁺ reversibly depolarized the resting membrane potential at concentrations greater than or equal to the apparent K_d for K⁺ conductance inhibition (2 mM). Depolarization consisted of a slow, maintained phase proportional to Cs⁺ concentration superimposed with 2- to 5-mV transient depolarizing events. Cs⁺ induced a Ca²⁺-dependent stimulation of aldosterone secretion in acutely dissociated cells, exhibiting an EC₅₀ of approximately 3 mM. Maximal Cs⁺-induced secretion was quantitatively similar to 1 nM ANG II- or 8 mM K⁺-induced secretion. Cs⁺-induced secretion was not additive with that of ANG II. K⁺ channel blockers that did not inhibit weakly voltage-dependent K⁺ channels at rest (quinidine, apamin, and charybdotoxin) did not cause depolarization or stimulate aldosterone secretion. Furthermore, charybdotoxin did not significantly affect ANG II-induced aldosterone secretion, indicating that Ca²⁺-dependent maxi-K⁺ channels did not contribute to the control of aldosterone secretion in acutely dissociated cells. These data strongly support involvement of weakly voltage-dependent K⁺ channels in ANG II-induced aldosterone secretion, but also implicate roles for other channel classes in controlling membrane potential during ANG II-induced aldosterone secretion.

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