Cation Permeability of Voltage-Gated Hair Cell Ca(2+) Channels of the Vertebrate Labyrinth

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.