Plenary Lecture
SUMOylation of Ion Channels at the Plasma Membrane Controls Neuronal Excitability

A decade ago, we were surprised to discover the small, ubiquitin-related modifier (SUMO) pathway operating outside the nucleus, regulating background K⁺ channels in the plasma membrane by direct, reversible covalent modification. Subsequently, we showed the pathway to control the activity of voltage-gated K⁺ channels that terminate action potentials. Now, we observe the pathway to modulate voltage-gated Na⁺ channels that initiate firing and, thereby, to mediate the early response of cerebellar neurons to acute hypoxic insult. Here, I describe our efforts to elucidate the mechanistic basis for these findings using electrophysiology and single particle spectroscopy to study cloned channels in experimental cells and native currents in primary neurons.