Alternate splicing in the cytosolic II-III loop and the carboxy terminus of human E-type voltage-gated Ca(2+) channels: electrophysiological characterization of isoforms.
There is growing evidence that Ca(v)2.3 (alpha1E, E-type) transcripts may encode the ion-conducting subunit of a subclass of R-type Ca(2+) channels, a heterogeneous group of channels by definition resistant to blockers of L-, N-, and P/Q-type Ca(2+) channels. To understand whether splice variation of Ca(v)2.3 contributes to the divergence of R-type channels, individual variants of Ca(v)2.3 were constructed and expressed in HEK-293 cells. With Ba(2+) as charge carrier, the tested biophysical properties were similar. In Ca(2+), the inactivation time course was slower and the recovery from short-term inactivation was faster; however, this occurred only in variants containing a 19-amino-acid-long insertion, which is typical for neuronal Ca(v)2.3 Ca(2+) channel subunits. This different Ca(2+) sensitivity is not responsible for the major differences between various R-type channels, and future studies might clarify its importance for in vivo synaptic or dendritic integration and the reasons for its loss in endocrine Ca(v)2.3 splice variants.
Pereverzev
Alexey
A
Institute of Neurophysiology, University of Cologne, Robert-Koch-Strasse 39, D-50931 Cologne, Germany.
Leroy
Jérôme
J
Krieger
Andreas
A
Malécot
Claire O
CO
Hescheler
Jürgen
J
Pfitzer
Gabriele
G
Klöckner
Udo
U
Schneider
Toni
T
D000200:Action Potentials / Q000235:genetics; D017398:Alternative Splicing / Q000502:physiology*; D000954:Antigens, Surface / Q000096:biosynthesis / Q000235:genetics; D015220:Calcium Channels / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D020908:Calcium Channels, R-Type; D027682:Cation Transport Proteins; D002460:Cell Line; D003600:Cytosol / Q000737:chemistry / Q000502:physiology; D006801:Humans; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D010446:Peptide Fragments / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D020033:Protein Isoforms / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000235:genetics; D050827:Syntaxin 1
D000954:Antigens, Surface; C423009:CACNA1E protein, human; D015220:Calcium Channels; D020908:Calcium Channels, R-Type; D027682:Cation Transport Proteins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D020033:Protein Isoforms; D050827:Syntaxin 1