title: Multiple structural elements contribute to voltage-dependent facilitation of neuronal alpha 1C (CaV1.2) L-type calcium channels.
abstract: Voltage- and frequency-dependent facilitation of calcium channel activity has been implicated in a number of key physiological processes. Various mechanisms have been proposed to mediate these regulations, including a switch between channel gating modes, voltage-dependent phosphorylation, and a voltage-dependent deinhibition of G-protein block. Studying such modulation on recombinant Ca channels expressed in oocytes, we previously reported that alpha(1C) L-type calcium channel contrast with non-L type Ca channels by its ability to exhibit facilitation by pre-depolarization (Voltage-dependent facilitation of a neuronal alpha(IC) L-type calcium channel, E. Bourinet et al., EMBO Journal, 1994; 13, 5032-5039). To further analyze this effect, we have investigated the molecular determinants which mediate the differences in voltage-dependent facilitation between "facilitable" alpha(1C) and "non facilitable" alpha(1E) calcium channels. We used a series of chimeras which combine the four transmembrane domains of the two channels. Results show that the four domains of alpha(1C) contribute to facilitation, with domain I being most critical. This domain is required but not sufficient alone to generate facilitation. The minimal requirement to observe the effect is the presence of domain I plus one of the three others. We conclude that similarly to activation gating, voltage-dependent facilitation of alpha(1C) is a complex process which involves multiple structural elements were domains I and III play the major role.
authors.affiliation: Physiopathologie des Canaux Ioniques, IGH CNRS UPR1142, 141 Rue de la Cardonille, 34396 Montpellier cedex 5, France.
authors.forename: C
authors.initials: C
authors.lastname: Altier
authors.forename: R L
authors.initials: RL
authors.lastname: Spaetgens
authors.forename: J
authors.initials: J
authors.lastname: Nargeot
authors.forename: E
authors.initials: E
authors.lastname: Bourinet
authors.forename: G W
authors.initials: GW
authors.lastname: Zamponi
mesh_terms: D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology; D015220:Calcium Channels / Q000737:chemistry / Q000502:physiology*; D020746:Calcium Channels, L-Type / Q000737:chemistry / Q000502:physiology*; D020908:Calcium Channels, R-Type; D027682:Cation Transport Proteins; D006801:Humans; D015640:Ion Channel Gating; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009865:Oocytes / Q000502:physiology; D018408:Patch-Clamp Techniques; D011758:Pyrroles / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014981:Xenopus
chemical_list: C423009:CACNA1E protein, human; D002120:Calcium Channel Agonists; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D020908:Calcium Channels, R-Type; D027682:Cation Transport Proteins; C419385:L-type calcium channel alpha(1C); D011758:Pyrroles; C071658:FPL 64176