Cation Permeability of Voltage-Gated Hair Cell Ca Channels of the Vertebrate Labyrinth.

Some hearing, vestibular, and vision disorders are imputable to voltage-gated Ca channels of the sensory cells. These channels convey a large Ca influx despite extracellular Na being 70-fold more concentrated than Ca; such high selectivity is lost in low Ca, and Na can permeate. Since the permeation properties and molecular identity of sensory Ca channels are debated, in this paper, we examine the Na current flowing through the L- and R-type Ca channels of labyrinth hair cells. Ion currents and cytosolic free Ca 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, 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. The deactivation of the R-type Na current was not accelerated, and its current amplitude increased by 2.3-fold in low Ca; 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 more strongly than that of R channel; furthermore, external Ca prevents nifedipine from perturbing the R selectivity filter.