Hyperpolarization-activated cyclic nucleotide-gated channels in pancreatic β-cell

Wasim El-Kholy, Patrick E. MacDonald, Jocelyn Manning Fox, Alpana Bhattacharjee, Tian Xue, Xiaodong Gao, Yi Zhang, Juliane Stieber, Ronald A. Li, Robert G. Tsushima, Michael B. Wheeler

Research output: Contribution to journalArticlepeer-review

Abstract

Hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels mediate the pacemaker current (Ih or If) observed in electrically rhythmic cardiac and neuronal cells. Here we describe a hyperpolarization-activated time-dependent cationic current, β-I h, in pancreatic β-cells. Transcripts for HCN1-4 were detected by RT-PCR and quantitative PCR in rat islets and MIN6 mouse insulinoma cells. β-Ih in rat β-cells and MIN6 cells displayed biophysical and pharmacological properties similar to those of HCN currents in cardiac and neuronal cells. Stimulation of cAMP production with forskolin/3-isobutyl-1- methylxanthine (50 μM) or dibutyryl-cAMP (1 mM) caused a significant rightward shift in the midpoint activation potential of β-Ih, whereas expression of either specific small interfering (si)RNA against HCN2 (siHCN2b) or a dominant-negative HCN channel (HCN1-AAA) caused a near-complete inhibition of time-dependent β-Ih. However, expression of siHCN2b in MIN6 cells had no affect on glucose-stimulated insulin secretion under normal or cAMP-stimulated conditions. Blocking β-Ih in intact rat islets also did not affect membrane potential behavior at basal glucose concentrations. Taken together, our experiments provide the first evidence for functional expression of HCN channels in the pancreatic β-cell.

Original languageEnglish (US)
Pages (from-to)753-764
Number of pages12
JournalMolecular Endocrinology
Volume21
Issue number3
DOIs
StatePublished - Mar 2007

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

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