On the role of TRPM1 desensitization in retinal signaling
MetadataShow full item record
Studies of retinal ON bipolar cells (BCs) reveal that prolonged light stimulation triggers a Ca2+ dependent desensitization of the synaptic current mediated by Trpm1, whose conductance is negatively regulated by a metabotropic receptor mGluR6. In light, the mGluR6 signaling pathway is inactivated and Trpm1 opens, allowing permeation of Na+ and Ca2+. The influx of Ca2+ in steady bright light produces negative feedback, termed desensitization, which reduces the amplitude of Trpm1 current. This observation led us to speculate that Trpm1 desensitization shapes the retinal output by repolarizing ON BC membrane and reducing transmitter release onto postsynaptic ganglion cells (GCs). One of the outcomes of this hypothesis is that desensitization produces transient responses in GCs to a sustained light stimulus. Here, evidence is provided in support of this hypothesis. In chapter 2, the Ca2+ dependence on Trpm1 desensitization was investigated by measuring the ON BC responses under variable strengths of presynaptic stimulus. The magnitude of desensitization and the subsequent recovery from desensitization were both highly correlated with the stimulus strength. In chapter 3, the functional role of Trpm1 desensitization was examined by analyzing post-synaptic responses from GCs while light responses were triggered in ON BCs. The responses in GCs were transient to a sustained stimulus, and abolishing Trpm1 desensitization increased the steady state component of the EPSC producing a sustained response. Feedback inhibition from amacrine cells also shapes the responses of GCs. However, feedback inhibition contributes to the initial phase of the EPSC by truncating the peak, while Trpm1 desensitization shapes the sustained component of the GC response. These results demonstrate that Trpm1 desensitization provides a mechanism to prevent continuous transmitter release in bright light to ensure that GCs remain responsive to other ON BCs within its receptive field.
- Theses and Dissertations