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The Journal of Neuroscience, January 1, 2002, 22(1):82-92
Identification and Characterization of Novel Human
Cav2.2 ( 1B) Calcium Channel Variants Lacking
the Synaptic Protein Interaction Site
Shuji
Kaneko1,
Conan B.
Cooper4,
Naoto
Nishioka1,
Hironobu
Yamasaki1,
Atsushi
Suzuki1,
Scott E.
Jarvis4,
Akinori
Akaike2,
Masamichi
Satoh3, and
Gerald W.
Zamponi4
Departments of 1 Neuropharmacology,
2 Pharmacology, and 3 Molecular Pharmacology,
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku,
Kyoto 606-8501, Japan, and 4 Department of Physiology and
Biophysics, University of Calgary, Calgary, T2N 4N1 Canada
The physical interaction between the presynaptic vesicle release
complex and the large cytoplasmic region linking domains II and III of
N-type (Cav2.2) calcium channel
 1B subunits is considered to be of
fundamental importance for efficient neurotransmission. By PCR analysis
of human brain cDNA libraries and IMR32 cell mRNA, we have isolated
novel N-type channel variants, termed Cav2.2- 1 and 2,
which lack large parts of the domain II-III linker region, including
the synaptic protein interaction site. They appear to be widely
expressed across the human CNS as indicated by RNase protection assays.
When expressed in tsA-201 cells, both novel variants formed
barium-permeable channels with voltage dependences and kinetics for
activation that were similar to those observed with the full-length
channel. All three channel types exhibited the hallmarks of prepulse
facilitation, which interestingly occurred independently of G-protein
  subunits. By contrast, the voltage dependence of steady-state
inactivation seen with both 1 and 2 channels was shifted toward
more depolarized potentials, and recovery from inactivation of 1 and
2 channels occurred more rapidly than that of the full-length
channel. Moreover, the 1 channel was dramatically less sensitive to
both  -conotoxin MVIIA and GVIA than either the 2 variant
or the full-length construct. Finally, the domain II-III linker region
of neither variant was able to effectively bind syntaxin in
vitro. These results suggest that the structure of the II-III
linker region is an important determinant of N-type channel function
and pharmacology. The lack of syntaxin binding hints at a unique
physiological function of these channels.
Key words:
human brain; class B calcium channel; alternative
splicing; synprint site; -conotoxins; syntaxin; G
Copyright © 2002 Society for Neuroscience 0270-6474/02/22182-11$05.00/0
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