Ionic mechanisms mediating oscillatory membrane potentials in wide-field retinal amacrine cells

Particular types of amacrine cells of the vertebrate retina show oscillatory membrane potentials (OMPs) in response to light stimulation. Historically it has been thought the oscillations arose as a result of circuit properties. In a previous study we found that in some amacrine cells, the ability to oscillate was an intrinsic property of the cell. Here we characterized the ionic mechanisms responsible for the oscillations in wide-field amacrine cells (WFACs) in an effort to better understand the functional properties of the cell. The OMPs were found to be calcium (Ca²⁺) dependent; blocking voltage-gated Ca²⁺ channels eliminated the oscillations, whereas elevating extracellular Ca²⁺ enhanced them. Strong intracellular Ca²⁺ buffering (10 mM EGTA or bis-(o-amino-phenoxy)-N,N,N′,N′-tetraacetic acid) eliminated any attenuation in the OMPs as well as a Ca²⁺-dependent inactivation of the voltage-gated Ca²⁺ channels. Pharmacological and immunohistochemical characterization revealed that WFACs express L- and N-type voltage-sensitive Ca²⁺ channels. Block of the L-type channels eliminated the OMPs, but ω-conotoxin GVIA did not, suggesting a different function for the N-type channels. The L-type channels in WFACs are functionally coupled to a set of calcium-dependent potassium (K_(Ca)) channels to mediate OMPs. The initiation of OMPs depended on penitrem-A-sensitive (BK) K_(Ca) channels, whereas their duration is under apamin-sensitive (SK) K_(Ca) channel control. The Ca²⁺ current is essential to evoke the OMPs and triggering the K_(Ca) currents, which here act as resonant currents, enhances the resonance as an amplifying current, influences the filtering characteristics of the cell membrane, and attenuates the OMPs via CDI of the L-type Ca²⁺ channel.