Abstract
Abstract: :
Purpose: Large conductance calcium activated potassium channels (BK) are commonly expressed in synaptic terminals, in close association with calcium channels and transmitter release machinery. In spiking neurons, BK channels have been found to reduce transmitter release by limiting membrane depolarization or in some cases increase transmitter release by increasing calcium channel driving force during repolarization. BK channels are also expressed at non–spiking ribbon synapses in the retina. However, their function at ribbon synapses is not clear. In this study we investigated BK channels' role in regulating synaptic transmission at the rod synapse. Methods: Whole cell patch–clamp recordings were made from isolated tiger salamander retinal neurons or neurons in dark–adapted retina slices. Results:BK channel current was recorded from isolated rods and this current could be blocked by 1 mM TEA or 100 nM Charybdotoxin. In rods that lost their synaptic terminals during dissociation, BK channel current was about 80 percent less than that of rods with synaptic terminals. This result suggests that most of the functional BK conductance in rods is associated with synaptic terminals. In dark adapted retinal slices, light evoked EPSCs in ON and OFF bipolar cells and horizontal cells were suppressed when BK channels were blocked. Holding current became more positive in horizontal and OFF bipolar cells and more negative in ON bipolar cells. These results suggest BK channels increase transmitter release in photoreceptors. However, BK channel blockers had little effect on rod light responses, indicating that BK channels affect synaptic transmission by a mechanism other than changing the rod’s voltage response to light. One possibility is that they affect synaptic calcium channel activity. Indeed, when rod BK channels were blocked, calcium current was suppressed and calcium channel activation shifted to more positive voltages. Increasing external K+ concentration to 10 mM enhanced calcium current in rods. This suggests that BK channels enhance calcium channel activity by increasing extracellular K+ concentration in the synaptic cleft. Conclusions: Contrary to a traditional function as an inhibitory channel, BK channels in photoreceptor terminals increase transmitter release by enhancing calcium channel current and shifting calcium channel activation to more negative voltages. Thus the synaptic transmission from photoreceptors to second order neurons is enhanced, and the light response amplitude transmitted to the second order neurons is amplified.
Keywords: ion channels • photoreceptors • synapse