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Cation Permeability of Voltage-Gated Hair Cell $Ca^{2+}$ Channels of the Vertebrate Labyrinth
| Content Provider | MDPI |
|---|---|
| Author | Martini, Marta Rispoli, Giorgio |
| Copyright Year | 2022 |
| Description | Some hearing, vestibular, and vision disorders are imputable to voltage-gated $Ca^{2+}$ channels of the sensory cells. These channels convey a large $Ca^{2+}$ influx despite extracellular $Na^{+}$ being 70-fold more concentrated than $Ca^{2+}$; such high selectivity is lost in low $Ca^{2+}$, and $Na^{+}$ can permeate. Since the permeation properties and molecular identity of sensory $Ca^{2+}$ channels are debated, in this paper, we examine the $Na^{+}$ current flowing through the L- and R-type $Ca^{2+}$ channels of labyrinth hair cells. Ion currents and cytosolic free $Ca^{2+}$ concentrations were simultaneously monitored in whole-cell recording synchronous to fast fluorescence imaging. L-type and R-type channels were present with different densities at selected sites. In 10 nM $Ca^{2+}$, the activation and deactivation time constants of the L-type $Na^{+}$ current were accelerated and its maximal amplitude increased by 6-fold compared to physiological $Ca^{2+}$. The deactivation of the R-type $Na^{+}$ current was not accelerated, and its current amplitude increased by 2.3-fold in low $Ca^{2+}$; moreover, it was partially blocked by nifedipine in a voltage- and time-dependent manner. In conclusion, L channel gating is affected by the ion species permeating the channel, and its selectivity filter binds $Ca^{2+}$ more strongly than that of R channel; furthermore, external $Ca^{2+}$ prevents nifedipine from perturbing the R selectivity filter. |
| Starting Page | 3786 |
| e-ISSN | 14220067 |
| DOI | 10.3390/ijms23073786 |
| Journal | International Journal of Molecular Sciences |
| Issue Number | 7 |
| Volume Number | 23 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2022-03-29 |
| Access Restriction | Open |
| Subject Keyword | International Journal of Molecular Sciences Patch Clamp Semi-circular Canals Ca2+ Channel Selectivity Ca2+ Current Nifedipine Ion Channels Voltage-sensitive Channels |
| Content Type | Text |
| Resource Type | Article |