Biophysical and pharmacological properties of the voltage-gated potassium current of human pancreatic β-cells

James Herrington, Manuel Sanchez, Denize Wunderler, Lizhen Yan, Randal M. Bugianesi, Ivy E. Dick, Sam A. Clark, Richard M. Brochu, Birgit T. Priest, Martin G. Kohler, Owen B. McManus

Research output: Contribution to journalArticle

Abstract

Voltage-gated potassium (Kv) currents of human pancreatic islet cells were studied by whole-cell patch clamp recording. On average, 75% of the cells tested were identified as β-cells by single cell, post-recording RT-PCR for insulin mRNA. In most cells, the dominant Kv current was a delayed rectifier. The delayed rectifier activated at potentials above - 20 mV and had a V1/2 for activation of -5.3 mV. Onset of inactivation was slow for a major component (τ = 3.2 s at +20 mV) observed in all cells; a smaller component (τ = 0.30 s) with an amplitude of ∼25% was seen in some cells. Recovery from inactivation had a τ of 2.5 s at -80 mV and steady-state inactivation had a V1/2 of -39 mV. In 12% of cells (21/182) a low-threshold, transient Kv current (A-current) was present. The A-current activated at membrane potentials above -40 mV, inactivated with a time constant of 18.5 ms at -20 mV, and had a V1/2 for steady-state inactivation of -52 mV. TEA inhibited total Kv current with an IC50 = 0.54 mM and PAC, a disubstituted cyclohexyl Kv channel inhibitor, inhibited with an IC50 = 0.57 μM. The total Kv current was insensitive to margatoxin (100 nM), agitoxin-2 (50 nM), kaliotoxin (50 nM) and ShK (50 nM). Hanatoxin (100 nM) inhibited total Kv current by 65% at +20 mV. Taken together, these data provide evidence of at least two distinct types of Kv channels in human pancreatic β-cells and suggest that more than one type of Kv channel may be involved in the regulation of glucose-dependent insulin secretion.

Original languageEnglish (US)
Pages (from-to)159-175
Number of pages17
JournalJournal of Physiology
Volume567
Issue number1
DOIs
StatePublished - Aug 15 2005
Externally publishedYes

ASJC Scopus subject areas

  • Physiology

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    Herrington, J., Sanchez, M., Wunderler, D., Yan, L., Bugianesi, R. M., Dick, I. E., Clark, S. A., Brochu, R. M., Priest, B. T., Kohler, M. G., & McManus, O. B. (2005). Biophysical and pharmacological properties of the voltage-gated potassium current of human pancreatic β-cells. Journal of Physiology, 567(1), 159-175. https://doi.org/10.1113/jphysiol.2005.089375