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• W4288448977 abstract "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 Ca²⁺ influx through voltage-gated Ca²⁺ (Ca_V) channels mediating L-type currents, the molecular identity of Ca_V channels in BCs is uncertain. Therefore, we combined molecular and functional analyses to determine the expression profiles of Ca_V α₁, β, and α₂δ 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_V subunit expression within the RB population from mice of either sex, and significantly, we discovered that transmission from RB synapses was mediated by Ca²⁺ influx through P/Q-type (Ca_V2.1) and N-type (Ca_V2.2) conductances as well as the previously-described L-type (Ca_V1) and T-type (Ca_V3) conductances. Furthermore, we found both Ca_V1.3 and Ca_V1.4 proteins located near presynaptic ribbon-type active zones in RB axon terminals, indicating that the L-type conductance is mediated by multiple Ca_V1 subtypes. Similarly, Ca_V3 α₁, β, and α₂δ 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_V subunit in individual cells. <b>SIGNIFICANCE STATEMENT</b> Bipolar cells (BCs) transmit photoreceptor output to inner retinal neurons. Although synaptic transmission from BC terminals is thought to rely almost exclusively on Ca²⁺ influx through L-type voltage-gated Ca²⁺ (Ca_V) channels, the molecular identity of Ca_V channels in BCs is uncertain. Here, we report unexpectedly high molecular diversity of Ca_V subunits in BCs. Transmission from rod bipolar (RB) cell synapses can be mediated by Ca²⁺ influx through P/Q-type (Ca_V2.1) and N-type (Ca_V2.2) conductances as well as the previously-described L-type (Ca_V1) and T-type (Ca_V3) conductances. Furthermore, Ca_V1, Ca_V3, β, and α₂δ 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." @default.
• W4288448977 created "2022-07-29" @default.
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• W4288448977 date "2022-07-27" @default.
• W4288448977 modified "2023-09-27" @default.
• W4288448977 title "Multiple Calcium Channel Types with Unique Expression Patterns Mediate Retinal Signaling at Bipolar Cell Ribbon Synapses" @default.
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• W4288448977 doi "https://doi.org/10.1523/jneurosci.0183-22.2022" @default.
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