Modulation of adenosine triphosphate-sensitive potassium channel and voltage-dependent calcium channel by activin a in HIT-T15 cells

Hideo Mogami, Makoto Kanzaki, Romi Nobusawa, You Qing Zhang, Megumi Furukawa, Itaru Kojima

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

The ATP-sensitive potassium channel (KATP channel) determines the membrane potential of pancreatic β-cells and plays a critical role in the regulation of insulin secretion. The present study was conducted to investigate the effect of activin A, a member of the transforming growth factor-β supergene family, on the KATP channel in HIT-T15 clonal hamster insulinoma cells. In an excised inside-out patch, ATP-sensitive currents with a single channel conductance of approximately 20 picosiemens were observed. In an outside-out patch, currents with identical unitary conductance were also observed. In either case, the currents were augmented by diazoxide and blocked by glibenclamide, verifying that they were KATP channel currents. When KATP channel currents were monitored in an outside-out patch, activin A added to the bath solution inhibited KATP channel currents. Upon removal of activin A, the KATP channel currents were restored, suggesting that the inhibition was not due simply to spontaneous disappearance of channel activity (run-down). The KATP channel activity was markedly reduced after the addition of activin A and was reversed by diazoxide. Besides the inhibition of KATP channel, activin A increased, in a perforated patch, the amplitude of the inward Ba2+ current in response to a depolarizing pulse from-40 to +10 mV. Under the current clamp condition, activin A induced gradual depolarization, followed by a burst of action potentials. Activin-mediated action potentials were accompanied by an elevation of the cytoplasmic free calcium concentration. These results indicate that activin A causes depolarization of the plasma membrane by inhibiting the activity of the KATP channel. In addition, activin A directly modulates the voltage-dependent calcium channel and augments calcium entry.

Original languageEnglish
Pages (from-to)2960-2966
Number of pages7
JournalEndocrinology
Volume136
Issue number7
DOIs
Publication statusPublished - 1995 Jul
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology

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