QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, January 11, 2006, 26(2):685-695; doi:10.1523/JNEUROSCI.4620-05.2006

This Article Full Text Full Text (PDF) Supplemental data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (26) Citing Articles via Google Scholar Google Scholar Articles by Mohapatra, D. P. Articles by Trimmer, J. S. Search for Related Content PubMed PubMed Citation Articles by Mohapatra, D. P. Articles by Trimmer, J. S.

 Previous Article  |  Next Article 

Cellular/Molecular
The Kv2.1 C Terminus Can Autonomously Transfer Kv2.1-Like Phosphorylation-Dependent Localization, Voltage-Dependent Gating, and Muscarinic Modulation to Diverse Kv Channels

Durga P. Mohapatra and James S. Trimmer

Department of Pharmacology, School of Medicine, University of California, Davis, California 95616

Modulation of K⁺ channels is widely used to dynamically regulate neuronal membrane excitability. The voltage-gated K⁺ channel Kv2.1 is an abundant delayed rectifier K⁺ (I_K) channel expressed at high levels in many types of mammalian central neurons where it regulates diverse aspects of membrane excitability. Neuronal Kv2.1 is constitutively phosphorylated, localized in high-density somatodendritic clusters, and has a relatively depolarized voltage dependence of activation. Here, we show that the clustering and voltage-dependent gating of endogenous Kv2.1 in cultured rat hippocampal neurons are modulated by cholinergic stimulation, a common form of neuromodulation. The properties of neuronal Kv2.1 are recapitulated in recombinant Kv2.1 expressed in human embryonic kidney 293 (HEK293) cells, but not COS-1 cells, because of cell background-specific differences in Kv2.1 phosphorylation. As in neurons, Kv2.1 in HEK293 cells is dynamically regulated by cholinergic stimulation, which leads to Ca²⁺/calcineurin-dependent dephosphorylation of Kv2.1, dispersion of channel clusters, and hyperpolarizing shifts in the voltage-dependent gating properties of the channel. Immunocytochemical, biochemical, and biophysical analyses of chimeric Kv channels show that the Kv2.1 cytoplasmic C-terminal domain can act as an autonomous domain sufficient to transfer Kv2.1-like clustering, voltage-dependent activation, and cholinergic modulation to diverse Kv channels. These findings provide novel mechanistic insights into cholinergic modulation of ion channels and regulation of the localization and voltage-dependent gating properties of the abundant neuronal Kv2.1 channel by cholinergic and other neuromodulatory stimuli.

Key words: Kv2.1; calcineurin; neuromodulation; acetylcholine; hippocampus; intracellular signaling; calcium

---

Received Oct 27, 2005; revised December 1, 2005; accepted December 5, 2005.

This article has been cited by other articles:

				A. Lvov, D. Greitzer, S. Berlin, D. Chikvashvili, S. Tsuk, I. Lotan, and I. Michaelevski Rearrangements in the Relative Orientation of Cytoplasmic Domains Induced by a Membrane-anchored Protein Mediate Modulations in Kv Channel Gating J. Biol. Chem., October 9, 2009; 284(41): 28276 - 28291. [Abstract] [Full Text] [PDF]

				E. Bocksteins, A. L. Raes, G. Van de Vijver, T. Bruyns, P.-P. Van Bogaert, and D. J. Snyders Kv2.1 and silent Kv subunits underlie the delayed rectifier K+ current in cultured small mouse DRG neurons Am J Physiol Cell Physiol, June 1, 2009; 296(6): C1271 - C1278. [Abstract] [Full Text] [PDF]

				M. Johannessen, S. Ramachandran, L. Riemer, A. Ramos-Serrano, A. E. Ruoho, and M. B. Jackson Voltage-gated sodium channel modulation by {sigma}-receptors in cardiac myocytes and heterologous systems Am J Physiol Cell Physiol, May 1, 2009; 296(5): C1049 - C1057. [Abstract] [Full Text] [PDF]

				L. Mckeown, M. P. Burnham, C. Hodson, and O. T. Jones Identification of an Evolutionarily Conserved Extracellular Threonine Residue Critical for Surface Expression and Its Potential Coupling of Adjacent Voltage-sensing and Gating Domains in Voltage-gated Potassium Channels J. Biol. Chem., October 31, 2008; 283(44): 30421 - 30432. [Abstract] [Full Text] [PDF]

				H. Misonou, S. M. Thompson, and X. Cai Dynamic Regulation of the Kv2.1 Voltage-Gated Potassium Channel during Brain Ischemia through Neuroglial Interaction J. Neurosci., August 20, 2008; 28(34): 8529 - 8538. [Abstract] [Full Text] [PDF]

				D. P. Mohapatra, D. F. Siino, and J. S. Trimmer Interdomain Cytoplasmic Interactions Govern the Intracellular Trafficking, Gating, and Modulation of the Kv2.1 Channel J. Neurosci., May 7, 2008; 28(19): 4982 - 4994. [Abstract] [Full Text] [PDF]

				K.-S. Park, J.-W. Yang, E. Seikel, and J. S. Trimmer Potassium Channel Phosphorylation in Excitable Cells: Providing Dynamic Functional Variability to a Diverse Family of Ion Channels Physiology, February 1, 2008; 23(1): 49 - 57. [Abstract] [Full Text] [PDF]

				K. M. S. O'Connell, J. D. Whitesell, and M. M. Tamkun Localization and mobility of the delayed-rectifer K+ channel Kv2.1 in adult cardiomyocytes Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H229 - H237. [Abstract] [Full Text] [PDF]

				M. M. Tamkun, K. M. S. O'Connell, and A. S. Rolig A cytoskeletal-based perimeter fence selectively corrals a sub-population of cell surface Kv2.1 channels J. Cell Sci., July 15, 2007; 120(14): 2413 - 2423. [Abstract] [Full Text] [PDF]

				D. Guan, T. Tkatch, D. J. Surmeier, W. E. Armstrong, and R. C. Foehring Kv2 subunits underlie slowly inactivating potassium current in rat neocortical pyramidal neurons J. Physiol., June 15, 2007; 581(3): 941 - 960. [Abstract] [Full Text] [PDF]

				H. Vacher, D. P. Mohapatra, H. Misonou, and J. S. Trimmer Regulation of Kv1 channel trafficking by the mamba snake neurotoxin dendrotoxin K FASEB J, March 1, 2007; 21(3): 906 - 914. [Abstract] [Full Text] [PDF]

				P. T. Redman, K. He, K. A. Hartnett, B. S. Jefferson, L. Hu, P. A. Rosenberg, E. S. Levitan, and E. Aizenman Apoptotic surge of potassium currents is mediated by p38 phosphorylation of Kv2.1 PNAS, February 27, 2007; 104(9): 3568 - 3573. [Abstract] [Full Text] [PDF]

				H. Misonou, M. Menegola, D. P. Mohapatra, L. K. Guy, K.-S. Park, and J. S. Trimmer Bidirectional Activity-Dependent Regulation of Neuronal Ion Channel Phosphorylation J. Neurosci., December 27, 2006; 26(52): 13505 - 13514. [Abstract] [Full Text] [PDF]

				K. M. S. O'Connell, A. S. Rolig, J. D. Whitesell, and M. M. Tamkun Kv2.1 potassium channels are retained within dynamic cell surface microdomains that are defined by a perimeter fence. J. Neurosci., September 20, 2006; 26(38): 9609 - 9618. [Abstract] [Full Text] [PDF]

				K.-S. Park, D. P. Mohapatra, H. Misonou, and J. S. Trimmer Graded regulation of the Kv2.1 potassium channel by variable phosphorylation. Science, August 18, 2006; 313(5789): 976 - 979. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help