Hair cell-specific splicing of mRNA for the α _1D subunit of voltage-gated Ca ²⁺ channels in the chicken’s cochlea

Abstract

one of the authors regrets that she inadvertently omitted references to the computer program and protein potential function that the authors used for their simulations of barnase cited above. The following sentence should have been the first sentence of the Methods section: Molecular dynamics simulations were performed with the program ENCAD (44) and the potential energy function of Levitt et al. (45).

Functional Interaction of Auxiliary Subunits and Synaptic Proteins With CaV1.3 May Impart Hair Cell Ca2+Current Properties

“…In agreement with earlier studies (Hudspeth and Lewis 1988;Martini et al 2000;Smotherman and Narins 1999;Zidanic and Fuchs 1995), the DHP-sensitive Ca 2ϩ current in hair cells has a rapid onset and inactivates slowly. Despite the fact that the channel has been identified as Ca V 1.3␣ 1 channel (Kollmar et al 1997a), the current profile of the expressed-channel in HEK 293 cells is in sharp contrast to that in hair cells. The Ca V 1.3␣ 1 -channel current not only activates more slowly than the hair-cell DHP-sensitive current, it also shows robust inactivation, which can be fit with two time constants of inactivation ( inact ; Table 1; Fig.…”

“…However, as expected, the magnitude of the current was small (0.5 ϩ 0.1 pA/pF, n ϭ 5). Furthermore, as suggested in a previous report, splice variants in the Ca V 1.3␣ 1 channel (Kollmar et al 1997b) may provide additional differences that would determine distinct properties of hair cell L-type channel currents. Thus reconstitution of the native hair cell Ca 2ϩ current phenotype may require the hair cell-specific splice variant channel as well as their auxiliary subunits and synaptic proteins.…”

“…In contrast to other Ca 2ϩ channels, wherein the heterologous expression of the pore-forming ␣ subunit closely mirrors the native channel current, the biophysical properties of the expressed Ca V 1.3 are quite distinct from typical hair cell Ca 2ϩ currents (Bell et al 2001;Koschak et al 2001;Mikami et al 1989;Seino et al 1992;Williams et al 1992;Xu and Lipscombe 2001). Although it has been suggested that splice variants of Ca V 1.3␣ 1 channel in the chick basilar papilla may suffice to confer the unique properties of the DHP-sensitive Ca 2ϩ currents in hair cells (Kollmar et al 1997b), in other systems, there is ample evidence to suggest that co-assembly of auxiliary ␤ and ␣ 2 ␦ subunits with the ␣ 1 subunit may contribute to the properties of the native Ca 2ϩ current. For example, co-expression of the ␣ 2 ␦ and ␤ subunits approximates the voltage dependence and kinetics of gating of ␣ 1 -subunit in the native cardiac Ca 2ϩ current properties, as well as enhances the level of expression of the channels (Lacerda et al 1991;Perez-Garcia et al 1995;Wei et al 2000).…”

“…The DHP-sensitive Ca 2ϩ channel in hair cells has been cloned from the chick basilar papilla and identified as ␣ 1D (Kollmar et al 1997a) or Ca V 1.3 ␣ 1 channel (Ertel et al 2000). In contrast to other Ca 2ϩ channels, wherein the heterologous expression of the pore-forming ␣ subunit closely mirrors the native channel current, the biophysical properties of the expressed Ca V 1.3 are quite distinct from typical hair cell Ca 2ϩ currents (Bell et al 2001;Koschak et al 2001;Mikami et al 1989;Seino et al 1992;Williams et al 1992;Xu and Lipscombe 2001).…”

Direct interaction with a nuclear protein and regulation of gene silencing by a variant of the Ca 2+ -channel β 4 subunit

“…The dominant voltage-gated Ca 2ϩ channels of cochlear hair cells exhibit unique molecular and functional properties (14)(15)(16). The channels are composed of ␣ 1D subunits containing three unusual segments and yield an L-type Ca 2ϩ current that has a relatively negative threshold of activation, rapid activation and deactivation kinetics, and little or no Ca 2ϩ -dependent inactivation.…”