Epinephrine-induced hyperpolarization of islet cells without K ATP channels

Andrea Sieg, Jiping Su, Alvaro Munoz, Michael Buchenau, Mitsuhiro Nakazaki, Lydia Aguilar-Bryan, Joseph Bryan, Susanne Ullrich

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

This study examines the effect of epinephrine, a known physiological inhibitor of insulin secretion, on the membrane potential of pancreatic islet cells from sulfonylurea receptor-1 (ABCC8)-null mice (Sur1KO), which lack functional ATP-sensitive K+ (KATP) channels. These channels have been argued to be activated by catecholamines, but epinephrine effectively inhibits insulin secretion in both Sur1KO and wild-type islets and in mice. Isolated Sur1KO β-cells are depolarized in both low (2.8 mmol/1) and high (16.7 mmol/1) glucose and exhibit Ca2+-dependent action potentials. Epinephrine hyperpolarizes Sur1KO β-cells, inhibiting their spontaneous action potentials. This effect, observed in standard whole cell patches, is abolished by pertussis toxin and blocked by BaCl2. The epinephrine effect is mimicked by clonidine, a selective α 2-adrenoceptor agonist and inhibited by α-yohimbine, an α2-antagonist. A selection of K+ channel inhibitors, tetraethylammonium, apamin, dendrotoxin, iberiotoxin, E-4130, chromanol 293B, and tertiapin did not block the epinephrine-induced hyperpolarization. Analysis of whole cell currents revealed an inward conductance of 0.11 ± 0.04 nS/pF (n = 7) and a TEA-sensitive outward conductance of 0.55 ± 0.08 nS/pF (n = 7) at -60 and 0 mV, respectively. Guanosine 5′-O -(3-thiotriphosphate) (100 μM) in the patch pipette did not significantly alter these currents or activate novel inward-rectifying K+ currents. We conclude that epinephrine can hyperpolarize β-cells in the absence of KATP channels via activation of low-conductance BaCl 2-sensitive K+ channels that are regulated by pertussis toxin-sensitive G proteins.

Original languageEnglish (US)
Pages (from-to)E463-E471
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume286
Issue number3 49-3
DOIs
StatePublished - Mar 2004

Keywords

  • ABCC8
  • Adenosine triphosphate-sensitive potassium channels
  • Insulin secretion
  • Membrane potential
  • Pertussis toxin
  • Sulfonylurea receptor-1 knockout mice

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Biochemistry

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