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

• Published in: International journal of molecular sciences Vol. 23; no. 7
• Main Authors: Martini, Marta, Rispoli, Giorgio
• Format: Journal Article
• Language: English
• Published: Switzerland 29-03-2022
• Subjects: Animals; Calcium - metabolism; Cations; Hair - metabolism; Nifedipine - pharmacology; Permeability; Sodium - metabolism; Vertebrates - metabolism; nifedipine; patch clamp; Ca2+ channel selectivity; semi-circular canals; Ca2+ current; ion channels; voltage-sensitive channels
• ISSN: 1422-0067

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.