State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, China.
Department of Biology, University of Maryland, College Park, Maryland 20742.
J Neurosci. 2022 Aug 24;42(34):6487-6505. doi: 10.1523/JNEUROSCI.0183-22.2022. Epub 2022 Jul 27.
Retinal bipolar cells (BCs) compose the canonical vertical excitatory pathway that conveys photoreceptor output to inner retinal neurons. Although synaptic transmission from BC terminals is thought to rely almost exclusively on Ca influx through voltage-gated Ca (Ca) channels mediating L-type currents, the molecular identity of Ca channels in BCs is uncertain. Therefore, we combined molecular and functional analyses to determine the expression profiles of Ca α, β, and αδ subunits in mouse rod bipolar (RB) cells, BCs from which the dynamics of synaptic transmission are relatively well-characterized. We found significant heterogeneity in Ca subunit expression within the RB population from mice of either sex, and significantly, we discovered that transmission from RB synapses was mediated by Ca influx through P/Q-type (Ca2.1) and N-type (Ca2.2) conductances as well as the previously-described L-type (Ca1) and T-type (Ca3) conductances. Furthermore, we found both Ca1.3 and Ca1.4 proteins located near presynaptic ribbon-type active zones in RB axon terminals, indicating that the L-type conductance is mediated by multiple Ca1 subtypes. Similarly, Ca3 α, β, and αδ subunits also appear to obey a "multisubtype" rule, i.e., we observed a combination of multiple subtypes, rather than a single subtype as previously thought, for each Ca subunit in individual cells. Bipolar cells (BCs) transmit photoreceptor output to inner retinal neurons. Although synaptic transmission from BC terminals is thought to rely almost exclusively on Ca influx through L-type voltage-gated Ca (Ca) channels, the molecular identity of Ca channels in BCs is uncertain. Here, we report unexpectedly high molecular diversity of Ca subunits in BCs. Transmission from rod bipolar (RB) cell synapses can be mediated by Ca influx through P/Q-type (Ca2.1) and N-type (Ca2.2) conductances as well as the previously-described L-type (Ca1) and T-type (Ca3) conductances. Furthermore, Ca1, Ca3, β, and αδ subunits appear to obey a "multisubtype" rule, i.e., a combination of multiple subtypes for each subunit in individual cells, rather than a single subtype as previously thought.
视网膜双极细胞 (BC) 构成了将光感受器输出传递到内视网膜神经元的经典垂直兴奋性通路。尽管从 BC 末梢的突触传递被认为几乎完全依赖于通过介导 L 型电流的电压门控 Ca (Ca) 通道的 Ca 内流，但 BC 中的 Ca 通道的分子身份尚不确定。因此，我们结合了分子和功能分析，以确定 Caα、β和αδ亚基在小鼠杆状双极 (RB) 细胞中的表达谱，从这些细胞中相对较好地描述了突触传递的动力学。我们发现，来自雄性和雌性小鼠的 RB 群体中的 Ca 亚基表达存在显著异质性，并且重要的是，我们发现 RB 突触的传递是通过 P/Q 型 (Ca2.1) 和 N 型 (Ca2.2) 电导以及先前描述的 L 型 (Ca1) 和 T 型 (Ca3) 电导的 Ca 内流介导的。此外，我们发现 Ca1.3 和 Ca1.4 蛋白都位于 RB 轴突末梢的突触前带状活跃区附近，这表明 L 型电导是由多种 Ca1 亚型介导的。同样，Ca3α、β和αδ亚基似乎也遵循“多亚型”规则，即我们观察到单个细胞中每种 Ca 亚基的多个亚型的组合，而不是以前认为的单个亚型。双极细胞 (BC) 将光感受器的输出传递到内视网膜神经元。尽管从 BC 末梢的突触传递被认为几乎完全依赖于通过介导 L 型电压门控 Ca (Ca) 通道的 Ca 内流，但 BC 中的 Ca 通道的分子身份尚不确定。在这里，我们报告了 BC 中 Ca 亚基出人意料的高分子多样性。来自杆状双极 (RB) 细胞突触的传递可以通过 Ca 内流通过 P/Q 型 (Ca2.1) 和 N 型 (Ca2.2) 电导以及先前描述的 L 型 (Ca1) 和 T 型 (Ca3) 电导来介导。此外，Ca1、Ca3、β和αδ亚基似乎遵循“多亚型”规则，即单个细胞中每个亚基的多种亚型的组合，而不是以前认为的单个亚型。
