Department of Biology, Animal Physiology/Neurobiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91058 Erlangen, Germany.
Department of Biology, Animal Physiology/Neurobiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91058 Erlangen, Germany
J Neurosci. 2022 Aug 17;42(33):6325-6343. doi: 10.1523/JNEUROSCI.1878-21.2022. Epub 2022 Jul 8.
It is a commonly accepted view that light stimulation of mammalian photoreceptors causes a graded change in membrane potential instead of developing a spike. The presynaptic Ca channels serve as a crucial link for the coding of membrane potential variations into neurotransmitter release. Ca1.4 L-type Ca channels are expressed in photoreceptor terminals, but the complete pool of Ca channels in cone photoreceptors appears to be more diverse. Here, we discovered, employing whole-cell patch-clamp recording from cone photoreceptor terminals in both sexes of mice, that their Ca currents are composed of low- (T-type Ca channels) and high- (L-type Ca channels) voltage-activated components. Furthermore, Ca channels exerted self-generated spike behavior in dark membrane potentials, and spikes were generated in response to light/dark transition. The application of fast and slow Ca chelators revealed that T-type Ca channels are located close to the release machinery. Furthermore, capacitance measurements indicated that they are involved in evoked vesicle release. Additionally, RT-PCR experiments showed the presence of Ca3.2 T-type Ca channels in cone photoreceptors but not in rod photoreceptors. Altogether, we found several crucial functions of T-type Ca channels, which increase the functional repertoire of cone photoreceptors. Namely, they extend cone photoreceptor light-responsive membrane potential range, amplify dark responses, generate spikes, increase intracellular Ca levels, and boost synaptic transmission. Photoreceptors provide the first synapse for coding light information. The key elements in synaptic transmission are the voltage-sensitive Ca channels. Here, we provide evidence that mouse cone photoreceptors express low-voltage-activated Ca3.2 T-type Ca channels in addition to high-voltage-activated L-type Ca channels. The presence of T-type Ca channels in cone photoreceptors appears to extend their light-responsive membrane potential range, amplify dark response, generate spikes, increase intracellular Ca levels, and boost synaptic transmission. By these functions, Ca3.2 T-type Ca channels increase the functional repertoire of cone photoreceptors.
人们普遍认为，光刺激哺乳动物光感受器会引起膜电位的分级变化，而不是产生尖峰。突触前 Ca 通道是将膜电位变化编码为神经递质释放的关键环节。Ca1.4 L 型 Ca 通道在光感受器末梢表达，但圆锥状光感受器中的完整 Ca 通道库似乎更加多样化。在这里，我们通过对雌雄小鼠圆锥状光感受器末梢进行全细胞膜片钳记录发现，它们的 Ca 电流由低（T 型 Ca 通道）和高（L 型 Ca 通道）电压激活成分组成。此外，Ca 通道在暗膜电位下产生自发尖峰行为，并且对光/暗转换产生响应而产生尖峰。快速和慢速 Ca 螯合剂的应用表明 T 型 Ca 通道靠近释放机制。此外，电容测量表明它们参与诱发囊泡释放。此外，RT-PCR 实验表明 Ca3.2 T 型 Ca 通道存在于圆锥状光感受器中，但不存在于杆状光感受器中。总的来说，我们发现 T 型 Ca 通道具有几个关键功能，这些功能增加了圆锥状光感受器的功能范围。具体而言，它们扩展了圆锥状光感受器光响应膜电位范围，放大暗反应，产生尖峰，增加细胞内 Ca 水平，并增强突触传递。光感受器为编码光信息提供了第一个突触。突触传递的关键要素是电压敏感的 Ca 通道。在这里，我们提供的证据表明，除了高电压激活的 L 型 Ca 通道外，小鼠圆锥状光感受器还表达低电压激活的 Ca3.2 T 型 Ca 通道。T 型 Ca 通道在圆锥状光感受器中的存在似乎扩展了它们的光响应膜电位范围，放大暗反应，产生尖峰，增加细胞内 Ca 水平，并增强突触传递。通过这些功能，Ca3.2 T 型 Ca 通道增加了圆锥状光感受器的功能范围。
