The Skok legacy and beyond: Molecular mechanisms of slow synaptic excitation in sympathetic ganglia

Vladimir Skok and his colleagues did much of the pioneering work on fast excitatory synaptic transmission in sympathetic ganglia and on nicotinic acetylcholine receptors that mediate fast transmission. I and my colleagues (including Alex Selyanko, one of Vladimir’s protégés) have studied the additional process of slow synaptic excitation that is mediated by the action of acetylcholine on muscarinic receptors. This results primarily from the closure of “M-channels,” a subset of voltage-gated potassium channels composed of Kv7.2 and Kv7.3 channel subunits. These channels require membrane phosphatidylinositol-4,5-bisphosphate (PIP₂) for their opening, and their closure by muscarinic receptor activation is now thought to result from the reduction in PIP₂ levels that follows receptor-induced PIP₂ hydrolysis. The dynamics of these two forms of synaptic excitation are compared. Neirofiziologiya/Neurophysiology, Vol. 39, Nos. 4/5, pp. 284–289, July–October, 2007.