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Dual effect of nitric oxide on ATP-sensitive K+ channels in rat pancreatic beta cells

Takaaki Sunouchi1, Kimiaki Suzuki, Koichi Nakayama

  • 1Department of Pharmacology, Graduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka, Japan.

Pflugers Archiv : European Journal of Physiology
|February 2, 2008
PubMed

Insights

Nitric oxide (NO) exhibits dual effects on rat beta cell KATP channels. Low concentrations inhibit via cGMP/protein kinase G, while high concentrations activate independently of cGMP.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Cell Physiology

Background:

  • Nitric oxide (NO) influences insulin secretion, with concentration-dependent stimulatory and inhibitory effects.
  • Understanding the precise mechanisms of NO's action on pancreatic beta cells is crucial for metabolic research.

Purpose of the Study:

  • To investigate the concentration-dependent effects of NO on ATP-sensitive potassium (KATP) channels in rat beta cells.
  • To elucidate the signaling pathways mediating the dual action of NO on KATP channels.

Main Methods:

  • Utilized patch clamp analysis to study KATP channel activity in rat beta cells.
  • Employed NOC7 as an NO donor at varying concentrations (0.5 microM and 10 microM).
  • Investigated the roles of soluble guanylate cyclase (ODQ) and protein kinase G (KT5823) inhibitors, and mitochondrial uncoupler (FCCP).

Main Results:

  • Low concentration NO (0.5 microM) suppressed diazoxide-activated KATP channels via a cGMP/protein kinase G-dependent pathway.
  • High concentration NO (10 microM) activated KATP channels through a cGMP-independent mechanism.
  • Both low and high concentration effects were observed in the same patch, demonstrating a dual regulatory role.

Conclusions:

  • Low-concentration NO inhibits beta cell KATP channels through the cGMP/protein kinase G pathway.
  • High-concentration NO activates beta cell KATP channels via a distinct, cGMP-independent mechanism.
  • These findings clarify the complex role of NO in regulating beta cell function and insulin secretion.

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