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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
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