Presynaptic “Cav 2.3 containing” E-type Ca2+ channels share dual roles during neurotransmitter release
(Kamp et al., 2005)

Ca2+ influx into excitable cells is a prerequisite for neurotransmitter release and regulated exocytosis (Ashcroft
et al, 1994;Yang and Berggren, 2005b). Within the group of 10 cloned voltage-gated Ca2+ channels, the Cav2.3-
containing E-type Ca2+ channels are involved in various physiological processes like neurotransmitter release
and exocytosis together with other voltage gated Ca2+ channels of the Cav1, Cav2, and Cav3 subfamily. However,
E-type Ca2+ channels also exhibit several subunit-specific features, most of which still remain poorly understood.
Cav2.3 containing R-type channels (here called “E-type channels”) are also located in presynaptic terminals
and interact with some synaptic vesicle proteins, the so called SNARE proteins although lacking the classical
synprint interaction site. E-type channels trigger exocytosis (Vajna et al, 2001;Pereverzev et al, 2002a;Pereverzev et al,
2002b;Schulla et al, 2003;Jing et al, 2005;Yang and Berggren, 2005a) and are also involved in long term Potentiation
 (Dietrich et al, 2003;Brenowitz and Regehr, 2003). Recently, it was shown that its interaction with the EF-hand motif
containing protein EFHC1 is involved in the etiology and pathogenesis of juvenile myoclonic epilepsy (JME)
(Suzuki et al, 2004).

References related to secretion and neurotransmitter release

Ashcroft,F.M., Proks,P., Smith,P.A., Ämmälä,C., Bokvist,K. & Rorsman,P. (1994) Stimulus-secretion coupling
in pancreatic b cells. J.Cell.Biochem., 55 Suppl., 54-65.

Brenowitz,S.D. & Regehr,W.G. (2003) "Resistant" channels reluctantly reveal their roles. Neuron, 39, 391-394.

Dietrich,D., Kirschstein,T., Kukley,M., Pereverzev,A., von der Brelie,C., Schneider,T. & Beck,H. (2003)
 Functional specialization of presynaptic Cav2.3 Ca2+ channels. Neuron, 39, 483-496.

Jing,X., Li,D.Q., Olofsson,C.S., Salehi,A., Surve,V.V., Caballero,J., Ivarsson,R., Lundquist,I., Pereverzev,A.,
 Schneider,T., Rorsman,P. & Renstrom,E. (2005) Ca(V)2.3 calcium channels control second-phase insulin
release. J.Clin.Invest, 115, 146-154.

Pereverzev,A., Mikhna,M., Vajna,R., Gissel,C., Henry,M., Weiergräber,M., Hescheler,J., Smyth,N. &
Schneider,T. (2002a) Disturbances in glucose-tolerance, insulin-release and stress-induced hyperglycemia
upon disruption of the Cav2.3 (a1E) subunit of voltage-gated Ca2+ channels. Mol.Endocrinol., 16, 884-895.

Pereverzev,A., Vajna,R., Pfitzer,G., Hescheler,J., Klockner,U. & Schneider,T. (2002b) Reduction of insulin
secretion in the insulinoma cell line INS-1 by overexpression of a Ca(v)2.3 (alpha1E) calcium channel
antisense cassette. Eur.J.Endocrinol., 146, 881-889.

Schulla,V., Renstrom,E., Feil,R., Feil,S., Franklin,I., Gjinovci,A., Jing,X.J., Laux,D., Lundquist,I.,
Magnuson,M.A., Obermuller,S., Olofsson,C.S., Salehi,A., Wendt,A., Klugbauer,N., Wollheim,C.B.,
Rorsman,P. & Hofmann,F. (2003) Impaired insulin secretion and glucose tolerance in beta cell-selective
Ca(v)1.2 Ca2+ channel null mice. EMBO J., 22, 3844-3854.

Suzuki,T., Delgado-Escueta,A.V., Aguan,K., Alonso,M.E., Shi,J., Hara,Y., Nishida,M., Numata,T.,
Medina,M.T., Takeuchi,T., Morita,R., Bai,D., Ganesh,S., Sugimoto,Y., Inazawa,J., Bailey,J.N., Ochoa,A.,
Jara-Prado,A., Rasmussen,A., Ramos-Peek,J., Cordova,S., Rubio-Donnadieu,F., Inoue,Y.,
Osawa,M., Kaneko,S., Oguni,H., Mori,Y. & Yamakawa,K. (2004) Mutations in EFHC1 cause juvenile myoclonic
epilepsy. Nat.Genet., 36, 842-849.

Vajna,R., Klockner,U., Pereverzev,A., Weiergraber,M., Chen,X., Miljanich,G., Klugbauer,N., Hescheler,J.,
Perez-Reyes,E. & Schneider,T. (2001) Functional coupling between 'R-type' Ca2+ channels and insulin
secretion in the insulinoma cell line INS-1. Eur.J.Biochem., 268, 1066-1075.

Yang,S.N. & Berggren,P.O. (2005a) CaV2.3 channel and PKClambda: new players in insulin secretion.
J.Clin.Invest, 115, 16-20.

Yang,S.N. & Berggren,P.O. (2005b) {beta}-Cell CaV channel regulation in physiology and pathophysiology.
Am.J.Physiol Endocrinol.Metab, 288, E16-E28.


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