A subset of cone bipolar cells expresses the Na⁺ channel SCN2A in the human retina

Some bipolar cells in the human retina are known to express voltage-gated Na⁺ channels. However, it is unclear which types of channels are expressed, and whether Na⁺ channel expression is limited to specific types of bipolar cells. In the present study, we examined the types of voltage-gated Na⁺ channels expressed in human bipolar cells and the morphology of bipolar cells with voltage-gated Na⁺ currents. To investigate the expression of voltage-gated Na⁺ channels in human bipolar cells, we examined whether Na⁺ channel transcripts could be detected in single bipolar cells using the reverse transcription polymerase chain reaction (RT-PCR) technique. The voltage-gated Na⁺ current was recorded from isolated bipolar cells using the patch-clamp recording technique. Types of bipolar cells that have the Na⁺ currents were investigated by analyzing their morphology after staining with Lucifer yellow. Using RT-PCR, the SCN2A Na⁺ channel was detected in 5 of 6 isolated bipolar cells. This suggests that a subset of human bipolar cells expresses the SCN2A Na⁺ channel. Under voltage-clamp conditions, depolarizing voltage steps induced a fast transient inward current in cone bipolar cells with axon terminal boutons that stratified at the ON layer, which includes the stratum 3, 4, and 5 of the inner plexiform layer (IPL, n = 2/11 cells). The fast transient inward current of isolated bipolar cells was blocked by 1 μM of tetrodotoxin (TTX), a voltage-gated Na⁺ channel blocker. No fast transient inward current was recorded with axon terminals that stratify at the OFF layer, which includes stratum 1 and 2 of the IPL (n = 4). Thus, a subset of ON cone bipolar cells at least expresses the putative voltage-gated Na⁺ channel SCN2A in the human retina. The Na⁺ channels in the bipolar cells may serve to amplify the release of neurotransmitter, glutamate, when membrane potential is rapidly depolarized and thereby selectively accelerating light responses.