A novel K+ current inhibited by adrenocorticotropic hormone and angiotensin II in adrenal cortical cells.

B Mlinar,B.A Biagi,J.J Enyeart

doi:10.1016/s0021-9258(18)52922-7

B Mlinar, B.A Biagi + Show 1 more

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https://doi.org/10.1016/s0021-9258(18)52922-7

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Abstract

Adrenocorticotropic hormone (ACTH) and angiotensin II (AII) are peptides that regulate the production of steroid hormones by cells of the adrenal cortex. The cellular mechanisms linking these peptides to corticosteroid hormone secretion are not understood. In patch clamp recordings from bovine adrenal zona fasciculata (AZF) cells, we have identified a novel cholera toxin-sensitive K+ current (IAC), which is potently inhibited by both ACTH and AII with respective EC50 values of 4.5 and 145 pM. These two peptides depolarize AZF cells with a temporal pattern and potency that parallels the inhibition of IAC. With the discovery of IAC, we have identified a common molecular target for both ACTH and AII. The convergent inhibition of IAC by these two peptides suggests a mechanism whereby biochemical signals originating at the cell membrane can be transduced to depolarization-dependent Ca2+ entry and steroid hormone secretion.

Highlights

Adrenocorticotropichormone (ACTH)and angiotensin I1 (AII)are peptides that regulate the productionof steroid hormones by cells of the adrenal cortex
ACTH(1-24), AII, GTP, MgATP, GDPPS, GTP-yS,cholera toxin,pertussistoxin,tetraethylammonium, 4-aminopyridine, and apamin were obtained from Sigma. a-Dendrotoxin was obtained from Alomone Laboratories (Jerusalem, Israel)
Channel opening had ceased (Fig. 4, B and D).The current- The discovery of a novel K+ channel that sets adrenal zona fasciculata (AZF) cell voltage relationship indicated that theACTH-sensitive chan- membrane potential while it is potentlyinhibited by both nel was outwardly rectifying with a major conductance state ACTH and AI1 suggests a specific mechanism for peptide of [60-65] picosiemens at potentials positive to +20 mV

Summary

Introduction

Adrenocorticotropichormone (ACTH)and angiotensin I1 (AII)are peptides that regulate the productionof steroid hormones by cells of the adrenal cortex. Expressed negligible A-type current indicated that IAC channels were open at the resting membrane potential of these this current was under the inhibitory control of an intracelcells (-71.1 mV) (Fig. 1C).

Results

Conclusion