title: Regulation of high-voltage-activated Ca2+channel function, trafficking, and membrane stability by auxiliary subunits.
abstract: Voltage-gated Ca2+(CaV) channels mediate Ca2+ions influx into cells in response to depolarization of the plasma membrane. They are responsible for initiation of excitation-contraction and excitation-secretion coupling, and the Ca2+that enters cells through this pathway is also important in the regulation of protein phosphorylation, gene transcription, and many other intracellular events. Initial electrophysiological studies divided CaVchannels into low-voltage-activated (LVA) and high-voltage-activated (HVA) channels. The HVA CaVchannels were further subdivided into L, N, P/Q, and R-types which are oligomeric protein complexes composed of an ion-conducting CaVα1subunit and auxiliary CaVα2δ, CaVβ, and CaVγsubunits. The functional consequences of the auxiliary subunits include altered functional and pharmacological properties of the channels as well as increased current densities. The latter observation suggests an important role of the auxiliary subunits in membrane trafficking of the CaVα1subunit. This includes the mechanisms by which CaVchannels are targeted to the plasma membrane and to appropriate regions within a given cell. Likewise, the auxiliary subunits seem to participate in the mechanisms that remove CaVchannels from the plasma membrane for recycling and/or degradation. Diverse studies have provided important clues to the molecular mechanisms involved in the regulation of CaVchannels by the auxiliary subunits, and the roles that these proteins could possibly play in channel targeting and membrane Stabilization.
authors.affiliation: Department of Cell Biology, Center for Research and Advanced Studies of the National Polytechnic Institute (Cinvestav-IPN), Mexico City, Mexico.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Felix
authors.affiliation: Department of Cell Biology, Center for Research and Advanced Studies of the National Polytechnic Institute (Cinvestav-IPN), Mexico City, Mexico.
authors.forename: Aida
authors.initials: A
authors.lastname: Calderón-Rivera
authors.affiliation: Department of Neuroscience, Brown University, Providence, RI, USA.
authors.forename: Arturo
authors.initials: A
authors.lastname: Andrade