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1 Department of Ion Channels, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA
2 Farmacología, Departamento de Medicina, Facultad de Medicina, Universidad de Oviedo, Julián Clavería 6, ES-33006, Oviedo, Spain
3 BetaGene Inc., 2600 North Stemmons Freeway, Suite 1, Dallas, TX 75207, USA
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 ß-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 V
for activation of –5.3 mV. Onset of inactivation was slow for a major component (
= 3.2 s at +20 mV) observed in all cells; a smaller component (
= 0.30 s) with an amplitude of 
25% was seen in some cells. Recovery from inactivation had a of 2.5 s at –80 mV and steady-state inactivation had a V 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 V 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 ß-cells and suggest that more than one type of Kv channel may be involved in the regulation of glucose-dependent insulin secretion.
(Received 26 April 2005;
accepted after revision 2 June 2005;
first published online 2 June 2005)
Corresponding author J. Herrington: Department of Ion Channels, Merck Research Laboratories, PO Box 2000, RY-80N-C31, Rahway, NJ 07065, USA. Email: james_herrington{at}merck.com
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