| Literature References | 1. WILLIAMS, M.E., BRUST. P.F., FELDMAN, D.H., PATTHI, S., SIMERSON, S.,
MAROUFI, A., MCCUE, A.F., VELICELBI, G., ELLIS, S.B. AND HARPOLD, M.M.
Structure and functional expression of an omega-conotoxin sensitive human
N-type calcium channel.
SCIENCE 257 389-395 (1992).
2. MORI, Y., FRIEDRICH, T., KIM, MS., MIKAMI, A., NAKAI, J., RUTH, P.,
BOSSE, E., HOFMANN, F., FLOCKERZI, V., FURUICHI, T., MIKOSHIBA, K.,
IMOTO, K., TANABE, T. AND NUMA, S.
Primary structure and functional expression from complementary DNA of a
brain calcium channel.
NATURE 350 398-402 (1991).
3. ASHCROFT, F.M.
Voltage-gated Ca2+ channels.
IN ION CHANNELS AND DISEASE, ACADEMIC PRESS, 2000, PP.161-183.
4. KOCH, W.J., ELLINOR, P.T. AND SCHWARTZ, A.
cDNA cloning of a dihydropyridine-sensitive calcium channel from rat aorta -
evidence for the existence of alternatively spliced forms.
J.BIOL.CHEM. 265(29) 17786-17791 (1990).
5. RANDALL, A.D. AND TSIEN, R.W.
Contrasting biophysical and pharmacological properties of T-type and R-type
calcium channels.
NEUROPHARMACOLOGY 36(7) 879-893 (1997).
6. FOEHRING, R.C., MERMELSTEIN, P.G., SONG, W., ULRICH, S. AND SURMEIER, D.J.
Unique properties of R-type calcium currents in neocortical and neostriatal
neurons.
J.NEUROPHYSIOL. 84(5) 2225-2236 (2000).
7. GASPARINI, S., KASYANOV, A.M., PIETROBON, D., VORONIN, L.L. AND
CHERUBINI, E.
Presynaptic R-type calcium channels contribute to fast excitatory synaptic
transmission in the rat hippocampus.
J.NEUROSCI. 21(22) 8715-8721 (2001).
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| Documentation | Calcium channel proteins are involved in the control of neurotransmitter
release from neurons [1], and play an important role in the regulation of a
variety of cellular functions, including membrane excitability, muscle
contraction and synaptic transmission [2]. Voltage-gated calcium channels
are classified as T, L, N, P, Q and R, and are distinguished by their
sensitivity to pharmacological blocks, single-channel conductance kinetics,
and voltage-dependence. On the basis of their voltage activation
properties, the voltage-gated calcium classes can be further divided into
two broad groups: the low (T-type) and high (L, N, P, Q and R-type)
threshold-activated channels [3].
Generally, the channel proteins are composed of 4 tightly-coupled subunits
(alpha-1, alpha-2, beta and gamma), the alpha-1 subunit from each creating
the pore for the import of extracellular calcium ions. The alpha-1 subunit
shares sequence characteristics with all voltage-dependent cation channels,
and exploits the same 6-helix bundle structural motif - in both sodium and
calcium channels, this motif is repeated 4 times within the sequence to give
a 24-helix bundle. Within each of these repeats, 5 of the transmembrane (TM)
segments (S1, S2, S3, S5, S6) are hydrophobic and one is positively charged
(S4) - the latter is characterised by charged amino acids at very third
position, and probably represents the voltage-sensor.
Several genes encoding alpha-1 subunits have been identified, each forming
a distinct electrophysiological channel [4]. R-type calcium channels are
composed of alpha-1E subunits and are found in a variety of neuronal
populations, such as cerebellar granule neurons and dendrites of hippocampal
pyrimidal neurons [5]. They are believed to play an important role in the
body's natural communication network, where they contribute to the
regulation of brain function by synaptic integration [6]. Their hypolarised
inactivation range and rapid kinetics of inactivation make R-type channels
more suited to providing a transient surge of Ca2+ influx [6,7].
RVDCCALPHA1 is a 6-element fingerprint that provides a signature for the
R-type voltage-dependent calcium channel alpha-1 subunit. The fingerprint
was derived from an initial alignment of 5 sequences: the motifs were drawn
from conserved regions spanning the N-terminal half of the alignment: motifs
1 and 2 lie in the extracellular region between TM domains 5 and 6 of repeat
I; motif 3 resides in the cytoplasmic region between TM domain 6 of repeat I
and TM domain 1 of repeat II; and motifs 4-6 span the cytoplasmic region
between TM domain 6 of repeat II and TM domain 1 of repeat III. A single
iteration on SPTR40_18f was required to reach convergence, no further
sequences being identified beyond the starting set.
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