Department of Neuroscience and Rehabilitation, Section of Physiology, University of Ferrara, Via Borsari 46, 44121 Ferrara, Italy.
Int J Mol Sci. 2022 Mar 29;23(7):3786. doi: 10.3390/ijms23073786.
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.
一些听力、前庭和视力障碍可归因于感觉细胞的电压门控 Ca 通道。这些通道尽管细胞外的 Na 浓度比 Ca 高 70 倍，但仍能传递大量的 Ca 内流；在低 Ca 和 Na 可渗透的情况下，这种高选择性会丧失。由于感觉 Ca 通道的渗透特性和分子身份存在争议，在本文中，我们研究了迷路毛细胞 L 型和 R 型 Ca 通道中的 Na 电流。在同步快速荧光成像的全细胞记录中，同时监测离子电流和细胞内游离 Ca 浓度。在选定的部位，L 型和 R 型通道以不同的密度存在。在 10 nM Ca 下，L 型 Na 电流的激活和失活时间常数加快，最大幅度增加了 6 倍，与生理 Ca 相比。R 型 Na 电流的失活没有加快，在低 Ca 下其电流幅度增加了 2.3 倍；此外，它被硝苯地平以电压和时间依赖的方式部分阻断。总之，L 通道的门控受到通过通道的离子种类的影响，其选择性过滤器与 R 通道相比更强烈地结合 Ca；此外，外部 Ca 可防止硝苯地平干扰 R 选择性过滤器。
