Expression of Voltage-Gated Potassium Channels in Human and Rhesus Pancreatic Islets
- Lizhen Yan1,
- David J. Figueroa2,
- Christopher P. Austin34,
- Yuan Liu5,
- Randal M. Bugianesi1,
- Robert S. Slaughter1,
- Gregory J. Kaczorowski1 and
- Martin G. Kohler1
- 1Department of Ion Channels, Merck Research Laboratories, Rahway, New Jersey
- 2Department of Molecular and Investigative Toxicology, Merck Research Laboratories, West Point, Pennsylvania
- 3Department of Neuroscience, Merck Research Laboratories, West Point, Pennsylvania
- 4National Human Genome Research Institute, Bethesda, Maryland
- 5Department of Bioinformatics, Merck Research Laboratories, West Point, Pennsylvania
- Address correspondence and reprint requests to Dr. Lizhen Yan or Dr. Martin G. Kohler, RY80N-C31, Department of Ion Channels, Merck Research Laboratories, Rahway, NJ 07065. E-mail: lizhen_yan{at}merck.com or martin_kohler{at}merck.com
Abstract
Voltage-gated potassium channels (Kv channels) are involved in repolarization of excitable cells. In pancreatic β-cells, prolongation of the action potential by block of delayed rectifier potassium channels would be expected to increase intracellular free calcium and to promote insulin release in a glucose-dependent manner. However, the specific Kv channel subtypes responsible for repolarization in β-cells, most importantly in humans, are not completely resolved. In this study, we have investigated the expression of 26 subtypes from Kv subfamilies in human islet mRNA. The results of the RT-PCR analysis were extended by in situ hybridization and/or immunohistochemical analysis on sections from human or Rhesus pancreas. Cell-specific markers were used to show that Kv2.1, Kv3.2, Kv6.2, and Kv9.3 are expressed in β-cells, that Kv3.1 and Kv6.1 are expressed in α-cells, and that Kv2.2 is expressed in δ-cells. This study suggests that more than one Kv channel subtype might contribute to the β-cell delayed rectifier current and that this current could be formed by heterotetramers of active and silent subunits.
- DAPI, 4,6-diamidino-2-phenylindole
- Em, membrane potential
- IA, fast transient current
- IDR, delayed rectifying current
- IHC, immunohistochemistry
- ISH, in situ hybridization
- KATP current, ATP-sensitive potassium current
- KCa current, calcium-activated potassium current
- Kv current, voltage-gated potassium current
- TM, transmembrane
Footnotes
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L.Y. and D.J.F. contributed equally to this article.
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- Accepted November 14, 2003.
- Received April 13, 2003.
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