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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Supplemental Table 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 (55) Citing Articles via Google Scholar Google Scholar Articles by Soong, T. W. Articles by Yue, D. T. Search for Related Content PubMed PubMed Citation Articles by Soong, T. W. Articles by Yue, D. T.

 Previous Article  |  Next Article 

The Journal of Neuroscience, December 1, 2002, 22(23):10142-10152

Systematic Identification of Splice Variants in Human P/Q-Type Channel ₁2.1 Subunits: Implications for Current Density and Ca²⁺-Dependent Inactivation

Tuck Wah Soong^{1, 2, 3}, Carla D. DeMaria³, Rebecca S. Alvania^{3, 4}, Larry S. Zweifel⁴, Mui Cheng Liang¹, Scott Mittman^{5, 6}, William S. Agnew⁵, and David T. Yue^{3, 4}

¹ National Neuroscience Institute, Singapore 308433, ² Department of Physiology, National University of Singapore, Singapore 119260, and Departments of ³ Biomedical Engineering, ⁴ Neuroscience, ⁵ Physiology, and ⁶ Anesthesiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

P/Q-type (Ca_v2.1) calcium channels support a host of Ca²⁺-driven neuronal functions in the mammalian brain. Alternative splicing of the main _1A (₁2.1) subunit of these channels may thereby represent a rich strategy for tuning the functional profile of diverse neurobiological processes. Here, we applied a recently developed "transcript-scanning" method for systematic determination of splice variant transcripts of the human ₁2.1 gene. This screen identified seven loci of variation, which together have never been fully defined in humans. Genomic sequence analysis clarified the splicing mechanisms underlying the observed variation. Electrophysiological characterization and a novel analytical paradigm, termed strength-current analysis, revealed that one focus of variation, involving combinatorial inclusion and exclusion of exons 43 and 44, exerted a primary effect on current amplitude and a corollary effect on Ca²⁺-dependent channel inactivation. These findings significantly expand the anticipated scope of functional diversity produced by splice variation of P/Q-type channels.

Key words: alternative splicing; P/Q-type calcium channel; _1A subunit; ₁2.1 subunit; transcript scanning; human brain; Ca²⁺-dependent inactivation; calmodulin

---

Copyright © 2002 Society for Neuroscience  0270-6474/02/222310142-11$05.00/0

This article has been cited by other articles:

				W. R. A. K. J. S. Rajapaksha, D. Wang, J. N. Davies, L. Chen, G. W. Zamponi, and T. E. Fisher Novel Splice Variants of Rat CaV2.1 That Lack Much of the Synaptic Protein Interaction Site Are Expressed in Neuroendocrine Cells J. Biol. Chem., June 6, 2008; 283(23): 15997 - 16003. [Abstract] [Full Text] [PDF]

				G. Cui, A. C. Meyer, I. Calin-Jageman, J. Neef, F. Haeseleer, T. Moser, and A. Lee Ca2+-binding proteins tune Ca2+-feedback to Cav1.3 channels in mouse auditory hair cells J. Physiol., December 15, 2007; 585(3): 791 - 803. [Abstract] [Full Text] [PDF]

				P. Liao, D. Yu, G. Li, T. F. Yong, J. L. Soon, Y. L. Chua, and T. W. Soong A Smooth Muscle Cav1.2 Calcium Channel Splice Variant Underlies Hyperpolarized Window Current and Enhanced State-dependent Inhibition by Nifedipine J. Biol. Chem., November 30, 2007; 282(48): 35133 - 35142. [Abstract] [Full Text] [PDF]

				J.C. Jen, T.D. Graves, E.J. Hess, M.G. Hanna, R.C. Griggs, R.W. Baloh, and the CINCH investigators Primary episodic ataxias: diagnosis, pathogenesis and treatment Brain, October 1, 2007; 130(10): 2484 - 2493. [Abstract] [Full Text] [PDF]

				A. T. Moritz, G. Newkirk, R. K. Powers, and M. D. Binder Facilitation of Somatic Calcium Channels Can Evoke Prolonged Tail Currents in Rat Hypoglossal Motoneurons J Neurophysiol, August 1, 2007; 98(2): 1042 - 1047. [Abstract] [Full Text] [PDF]

				R. C. E. Wykes, C. S. Bauer, S. U. Khan, J. L. Weiss, and E. P. Seward Differential Regulation of Endogenous N- and P/Q-Type Ca2+ Channel Inactivation by Ca2+/Calmodulin Impacts on Their Ability to Support Exocytosis in Chromaffin Cells J. Neurosci., May 9, 2007; 27(19): 5236 - 5248. [Abstract] [Full Text] [PDF]

				D. Chaudhuri, J. B. Issa, and D. T. Yue Elementary Mechanisms Producing Facilitation of Cav2.1 (P/Q-type) Channels J. Gen. Physiol., April 30, 2007; 129(5): 385 - 401. [Abstract] [Full Text] [PDF]

				K. Dunlap Calcium Channels Are Models of Self-Control J. Gen. Physiol., April 30, 2007; 129(5): 379 - 383. [Full Text] [PDF]

				H. Chen and E. S. Piedras-Renteria Altered frequency-dependent inactivation and steady-state inactivation of polyglutamine-expanded {alpha}1A in SCA6 Am J Physiol Cell Physiol, March 1, 2007; 292(3): C1078 - C1086. [Abstract] [Full Text] [PDF]

				E. W. Tringham, C. E. Payne, J. R. B. Dupere, and M. M. Usowicz Maturation of rat cerebellar Purkinje cells reveals an atypical Ca2+ channel current that is inhibited by {omega}-agatoxin IVA and the dihydropyridine (-)-(S)-Bay K8644 J. Physiol., February 1, 2007; 578(3): 693 - 714. [Abstract] [Full Text] [PDF]

				P. S. Yang, B. A. Alseikhan, H. Hiel, L. Grant, M. X. Mori, W. Yang, P. A. Fuchs, and D. T. Yue Switching of Ca2+-Dependent Inactivation of CaV1.3 Channels by Calcium Binding Proteins of Auditory Hair Cells. J. Neurosci., October 18, 2006; 26(42): 10677 - 10689. [Abstract] [Full Text] [PDF]

				Y. Shen, D. Yu, H. Hiel, P. Liao, D. T. Yue, P. A. Fuchs, and T. W. Soong Alternative Splicing of the CaV1.3 Channel IQ Domain, a Molecular Switch for Ca2+-Dependent Inactivation within Auditory Hair Cells. J. Neurosci., October 18, 2006; 26(42): 10690 - 10699. [Abstract] [Full Text] [PDF]

				A. J. Castiglioni, J. Raingo, and D. Lipscombe Alternative splicing in the C-terminus of CaV2.2 controls expression and gating of N-type calcium channels J. Physiol., October 1, 2006; 576(1): 119 - 134. [Abstract] [Full Text] [PDF]

				H. B. Kordasiewicz, R. M. Thompson, H. B. Clark, and C. M. Gomez C-termini of P/Q-type Ca2+ channel {alpha}1A subunits translocate to nuclei and promote polyglutamine-mediated toxicity Hum. Mol. Genet., May 15, 2006; 15(10): 1587 - 1599. [Abstract] [Full Text] [PDF]

				C.-J. Jeng, Y.-T. Chen, Y.-W. Chen, and C.-Y. Tang Dominant-negative effects of human P/Q-type Ca2+ channel mutations associated with episodic ataxia type 2 Am J Physiol Cell Physiol, April 1, 2006; 290(4): C1209 - C1220. [Abstract] [Full Text] [PDF]

				L. Kreiner and A. Lee Endogenous and Exogenous Ca2+ Buffers Differentially Modulate Ca2+-dependent Inactivation of CaV2.1 Ca2+ Channels J. Biol. Chem., February 24, 2006; 281(8): 4691 - 4698. [Abstract] [Full Text] [PDF]

				S. Kanumilli, E. W. Tringham, C. Elizabeth Payne, J. R. B. Dupere, K. Venkateswarlu, and M. M. Usowicz Alternative splicing generates a smaller assortment of CaV2.1 transcripts in cerebellar Purkinje cells than in the cerebellum Physiol Genomics, January 12, 2006; 24(2): 86 - 96. [Abstract] [Full Text] [PDF]

				P. Liao, T. F. Yong, M. C. Liang, D. T. Yue, and T. W. Soong Splicing for alternative structures of Cav1.2 Ca2+ channels in cardiac and smooth muscles Cardiovasc Res, November 1, 2005; 68(2): 197 - 203. [Abstract] [Full Text] [PDF]

				J. M. Nerbonne and R. S. Kass Molecular Physiology of Cardiac Repolarization Physiol Rev, October 1, 2005; 85(4): 1205 - 1253. [Abstract] [Full Text] [PDF]

				D. Chaudhuri, B. A. Alseikhan, S. Y. Chang, T. W. Soong, and D. T. Yue Developmental Activation of Calmodulin-Dependent Facilitation of Cerebellar P-Type Ca2+ Current J. Neurosci., September 7, 2005; 25(36): 8282 - 8294. [Abstract] [Full Text] [PDF]

				C. F. Barrett, Y.-Q. Cao, and R. W. Tsien Gating Deficiency in a Familial Hemiplegic Migraine Type 1 Mutant P/Q-type Calcium Channel J. Biol. Chem., June 24, 2005; 280(25): 24064 - 24071. [Abstract] [Full Text] [PDF]

				Q. Hu, H. Saegusa, Y. Hayashi, and T. Tanabe The carboxy-terminal tail region of human Cav2.1 (P/Q-type) channel is not an essential determinant for its subcellular localization in cultured neurones Genes Cells, February 1, 2005; 10(2): 87 - 96. [Abstract] [Full Text] [PDF]

				P. Liao, D. Yu, S. Lu, Z. Tang, M. C. Liang, S. Zeng, W. Lin, and T. W. Soong Smooth Muscle-selective Alternatively Spliced Exon Generates Functional Variation in Cav1.2 Calcium Channels J. Biol. Chem., November 26, 2004; 279(48): 50329 - 50335. [Abstract] [Full Text] [PDF]

				Z. Z. Tang, M. C. Liang, S. Lu, D. Yu, C. Y. Yu, D. T. Yue, and T. W. Soong Transcript Scanning Reveals Novel and Extensive Splice Variations in Human L-type Voltage-gated Calcium Channel, Cav1.2 {alpha}1 Subunit J. Biol. Chem., October 22, 2004; 279(43): 44335 - 44343. [Abstract] [Full Text] [PDF]

				D. Chaudhuri, S.-Y. Chang, C. D. DeMaria, R. S. Alvania, T. W. Soong, and D. T. Yue Alternative Splicing as a Molecular Switch for Ca2+/Calmodulin-Dependent Facilitation of P/Q-Type Ca2+ Channels J. Neurosci., July 14, 2004; 24(28): 6334 - 6342. [Abstract] [Full Text] [PDF]

				E Mantuano, L Veneziano, M Spadaro, P Giunti, S Guida, M G Leggio, L Verriello, N Wood, C Jodice, and M Frontali Clusters of non-truncating mutations of P/Q type Ca2+ channel subunit Cav2.1 causing episodic ataxia 2 J. Med. Genet., June 1, 2004; 41(6): e82 - e82. [Full Text] [PDF]

				M. X. Mori, M. G. Erickson, and D. T. Yue Functional Stoichiometry and Local Enrichment of Calmodulin Interacting with Ca2+ Channels Science, April 16, 2004; 304(5669): 432 - 435. [Abstract] [Full Text] [PDF]

				K. Jurkat-Rott and F. Lehmann-Horn The impact of splice isoforms on voltage-gated calcium channel {alpha}1 subunits J. Physiol., February 1, 2004; 554(3): 609 - 619. [Abstract] [Full Text] [PDF]

				S. C. Stotz, S. E. Jarvis, and G. W. Zamponi Functional roles of cytoplasmic loops and pore lining transmembrane helices in the voltage-dependent inactivation of HVA calcium channels J. Physiol., January 15, 2004; 554(2): 263 - 273. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help