![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Department of Applied Physiology, University of Ulm, Ulm, Germany (O.H.W., V.V., F.L.-H., S.G.); Institute for Human Genetics and Anthropology, Albert-Ludwigs-University, Freiburg, Germany (O.H.W., D.J.M.-R.); Division of Human Genetics and Department of Pediatrics (J.J.G.), Department of Physiology and Biophysics (H.T., F.I., J.J.G.); and Department of Psychiatry and Human Behavior (H.T.), University of California at Irvine, Irvine, California; and King Faisal Medical Center, Riyadh, Saudi Arabia (F.I.)
We have isolated an hSK3 isoform from a human embryonic cDNA library that we have named hSK3_ex4. This isoform contains a 15 amino acid insertion within the S5 to P-loop segment. Transcripts encoding hSK3_ex4 are coexpressed at lower levels with hSK3 in neuronal as well as in non-neuronal tissues. To investigate the pharmacokinetic properties of hSK3_ex4, we expressed the isoforms hSK3 and hSK3_ex4 in tsA cells. Both isoforms were similarly activated by cytosolic Ca2+ (hSK3, EC50 = 0.91 ± 0.4 µM; hSK3_ex4, EC50 = 0.78 ± 0.2 µM) and by 1-ethyl-2-benzimidazolinone (hSK3, EC50 = 0.17 mM; hSK3_ex4, 0.19 mM). They were both blocked by tetraethylammonium (hSK3, Kd = 2.2 mM; hSK3_ex4, 2.6 mM) and showed similar permeabilities relative to K+ for Cs+ (hSK3, 0.17 ± 0.04, n = 3; hSK3_ex4, 0.17 ± 0.05, n = 3) and Rb+ (hSK3, 0.79 ± 0.04, n = 3; hSK3_ex4, 0.8 ± 0.07, n = 3). Ba2+ blocked both isoforms, and in both cases, the block was strongest at hyperpolarizing membrane potentials. However, the voltage-dependence of hSK3 was stronger than that of hSK3_ex4. The most obvious distinguishing feature of this new isoform was that whereas hSK3 was blocked by apamin (Kd = 0.8 nM), scyllatoxin (Kd = 2.1 nM), and d-tubocurarine (Kd = 33.4 µM), hSK3_ex4 was not affected by apamin up to 100 nM, scyllatoxin up to 500 nM, and d-tubocurarine up to 500 µM. So far, isoform hSK3_ex4 forms the only small-conductance calcium-activated potassium (SK) channels, which are insensitive to the classic SK blockers.
Received July 16, 2003; accepted November 24, 2003.
Address correspondence to: Dr. Stephan Grissmer, Department of Applied Physiology, University of Ulm, Albert-Einstein-Allee 11, D-89081 Ulm, Germany. E-mail: stephan.grissmer{at}medizin.uni-ulm.de
This article has been cited by other articles:
|
|
 |
|
  N. Gu, H. Hu, K. Vervaeke, and J. F. Storm SK (KCa2) Channels Do Not Control Somatic Excitability in CA1 Pyramidal Neurons But Can Be Activated by Dendritic Excitatory Synapses and Regulate Their Impact J Neurophysiol, November 1, 2008; 100(5): 2589 - 2604. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Nolting, T. Ferraro, D. D'hoedt, and M. Stocker An Amino Acid Outside the Pore Region Influences Apamin Sensitivity in Small Conductance Ca2+-activated K+ Channels J. Biol. Chem., February 9, 2007; 282(6): 3478 - 3486. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Zhang, K. Houamed, S. Kupershmidt, D. Roden, and L. S. Satin Pharmacological Properties and Functional Role of Kslow Current in Mouse Pancreatic {beta}-Cells: SK Channels Contribute to Kslow Tail Current and Modulate Insulin Secretion J. Gen. Physiol., September 26, 2005; 126(4): 353 - 363. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Gu, K. Vervaeke, H. Hu, and J. F Storm Kv7/KCNQ/M and HCN/h, but not KCa2/SK channels, contribute to the somatic medium after-hyperpolarization and excitability control in CA1 hippocampal pyramidal cells J. Physiol., August 1, 2005; 566(3): 689 - 715. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
