Sulfonylurea Receptor Pharmacology Alters the Performance of Two Central Pattern Generating Circuits in Cancer...

Neuronal activity and energy supply must maintain a fine balance for neuronal fitness. Various channels of communication between the two could impact network output in different ways. Sulfonylurea receptors (SURs) are a modification of ATP-binding cassette proteins that confer ATP-dependent gating on their associated ion channels. They are widely expressed and link metabolic states directly to neuronal activity. The role they play varies in different circuits, both enabling bursting and inhibiting activity in pathological conditions. The crab, Cancer borealis, has central pattern generators (CPGs) that fire in rhythmic bursts nearly constantly and it is unknown how energy availability influences these networks. The pyloric network of the stomatogastric ganglion and the cardiac ganglion (CG) control rhythmic contractions of the foregut and heart, respectively. Known SUR agonists and antagonists produce opposite effects in the two CPGs. Pyloric rhythm activity completely stops in the presence of a SUR agonist, and activity increases in SUR blockers. This results from a decrease in the excitability of pyloric dilator neurons, which are a part of the pacemaker kernel. The neurons of the CG, paradoxically, increase firing within bursts in SUR agonists, and bursting slows in SUR antagonists. Analyses of the agonist-affected conductance properties present biophysical effects that do not trivially match those of mammalian SUR-dependent conductances. We suggest that SUR-associated conductances allow different neurons to respond to energy states in different ways through a common mechanism.