 |
 Previous Article | Next Article 
The Journal of Neuroscience, July 1, 2000, 20(13):4769-4775
Alternative Splicing in the Cytoplasmic II-III Loop of the
N-Type Ca Channel  1B Subunit: Functional Differences Are
 Subunit-Specific
Jennifer Qian
Pan and
Diane
Lipscombe
Department of Neuroscience, Brown University, Providence, Rhode
Island 02912
Structural diversity of voltage-gated Ca channels underlies much of
the functional diversity in Ca signaling in neurons. Alternative splicing is an important mechanism for generating structural variants within a single gene family. In this paper, we show the expression pattern of an alternatively spliced 21 amino acid encoding exon in the
II-III cytoplasmic loop region of the N-type Ca channel  1B subunit and assess its functional impact.
Exon-containing 1B mRNA dominated in sympathetic ganglia
and was present in ~50% of 1B mRNA in spinal cord and
caudal regions of the brain and in the minority of
1B mRNA in neocortex, hippocampus, and cerebellum (<20%). The II-III loop exon affected voltage-dependent inactivation of the N-type Ca channel. Steady-state inactivation curves were shifted
to more depolarized potentials without affects on either the rate or voltage dependence of channel opening.
Differences in voltage-dependent inactivation between 1B
splice variants were most clearly manifested in the presence of Ca
channel  1b or 4, rather than
2a or 3, subunits. Our results
suggest that exon-lacking 1B splice variants that
associate with 1b and 4 subunits will be
susceptible to voltage-dependent inactivation at voltages in the range
of neuronal resting membrane potentials ( 60 to 80 mV). In contrast,
1B splice variants that associate with either
2a or 3 subunits will be relatively
resistant to inactivation at these voltages. The potential to mix and
match multiple 1B splice variants and subunits
probably represents a mechanism for controlling the plasticity of
excitation-secretion coupling at different synapses.
Key words:
N-type calcium channel; 1 subunit; regulated alternative splicing; intracellular loop II-III; genomic
analysis; tissue distribution; subunit
Copyright © 2000 Society for Neuroscience 0270-6474/00/20134769-07$05.00/0
This article has been cited by other articles:
|
|
|
|
 
X. X. Chi, B. S. Schmutzler, J. M. Brittain, Y. Wang, C. M. Hingtgen, G. D. Nicol, and R. Khanna
Regulation of N-type voltage-gated calcium channels (Cav2.2) and transmitter release by collapsin response mediator protein-2 (CRMP-2) in sensory neurons
J. Cell Sci.,
December 1, 2009;
122(23):
4351 - 4362.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Altier, C. S. Dale, A. E. Kisilevsky, K. Chapman, A. J. Castiglioni, E. A. Matthews, R. M. Evans, A. H. Dickenson, D. Lipscombe, N. Vergnolle, et al.
Differential Role of N-Type Calcium Channel Splice Isoforms in Pain
J. Neurosci.,
June 13, 2007;
27(24):
6363 - 6373.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Zhang, B. Star, W. R. A. K. J. S. Rajapaksha, and T. E. Fisher
Dehydration increases L-type Ca2+ current in rat supraoptic neurons
J. Physiol.,
April 1, 2007;
580(1):
181 - 193.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Mameli, P. A. Zamudio, M. Carta, and C. F. Valenzuela
Developmentally Regulated Actions of Alcohol on Hippocampal Glutamatergic Transmission
J. Neurosci.,
August 31, 2005;
25(35):
8027 - 8036.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Lin, S. I. McDonough, and D. Lipscombe
Alternative Splicing in the Voltage-Sensing Region of N-Type CaV2.2 Channels Modulates Channel Kinetics
J Neurophysiol,
November 1, 2004;
92(5):
2820 - 2830.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Thaler, A. C. Gray, and D. Lipscombe
Cumulative inactivation of N-type CaV2.2 calcium channels modified by alternative splicing
PNAS,
April 13, 2004;
101(15):
5675 - 5679.
[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]
|
|
|
|
|
|
|
J. M. Schjott, S.-C. Hsu, and M. R. Plummer
The Neuronal {beta}4 Subunit Increases the Unitary Conductance of L-type Voltage-gated Calcium Channels in PC12 Cells
J. Biol. Chem.,
September 5, 2003;
278(36):
33936 - 33942.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. K. Hajela, S.-Q. Peng, and W. D. Atchison
Comparative Effects of Methylmercury and Hg2+ on Human Neuronal N- and R-Type High-Voltage Activated Calcium Channels Transiently Expressed in Human Embryonic Kidney 293 Cells
J. Pharmacol. Exp. Ther.,
September 1, 2003;
306(3):
1129 - 1136.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Peng, R. K. Hajela, and W. D. Atchison
Characteristics of Block by Pb2+ of Function of Human Neuronal L-, N-, and R-Type Ca2+ Channels Transiently Expressed in Human Embryonic Kidney 293 Cells
Mol. Pharmacol.,
December 1, 2002;
62(6):
1418 - 1430.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Kawasaki, S. C. Collins, and R. W. Ordway
Synaptic Calcium-Channel Function in Drosophila: Analysis and Transformation Rescue of Temperature-Sensitive Paralytic and Lethal Mutations of Cacophony
J. Neurosci.,
July 15, 2002;
22(14):
5856 - 5864.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. D. Helton and W. A. Horne
Alternative Splicing of the beta 4 Subunit Has alpha 1 Subunit Subtype-Specific Effects on Ca2+ Channel Gating
J. Neurosci.,
March 1, 2002;
22(5):
1573 - 1582.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Kaneko, C. B. Cooper, N. Nishioka, H. Yamasaki, A. Suzuki, S. E. Jarvis, A. Akaike, M. Satoh, and G. W. Zamponi
Identification and Characterization of Novel Human Cav2.2 (alpha 1B) Calcium Channel Variants Lacking the Synaptic Protein Interaction Site
J. Neurosci.,
January 1, 2002;
22(1):
82 - 92.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Brudno, M. S. Gelfand, S. Spengler, M. Zorn, I. Dubchak, and J. G. Conboy
Computational analysis of candidate intron regulatory elements for tissue-specific alternative pre-mRNA splicing
Nucleic Acids Res.,
June 1, 2001;
29(11):
2338 - 2348.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
