Mechanisms of nociceptive signal coding: Role of slow sodium channels

Abstract

321 Using whole-cell patch-clamp method, the rat DRG nociceptive neuron membrane was investigated. Extracellular ouabain applications lead to a decrease of the effective charge transfer in the activation gating system of the slow sodium channels (TTX r , Na v 1.8). Ouabain concentration–effective charge transfer (dose– response) dependence has U-like shape after extracellular ouabain application. Left branch of this dependence is monotonous in the range from 100 pM to 1 μ M (K d = 3 nM). Quantum-chemical calculations have shown that the ouabain molecule could effectively form the chelate complex with free calcium ion. As a result, the equilibrium geometry of this complex changes and the probable consequence of this binding is the fact that this complex better fits the transducer site of the Na + ,K + -ATPase. Besides, the chelate complex should specifically activate this transducer site due to the ionionic binding. Less specific free (without calcium) ouabain higher concentration binding takes place at the different Na + ,K + -ATPase site that probably controls its pumping function. Heterogeneity of the ouabain binding sites could explain the U-like shape of the dose– response function under investigation. The inflammatory pain test shows that injections of ouabain at low concentration (i.p., 0.3 mg/kg) lead to pain relief. We hypothesize that physiological role of the endogenous ouabain results in the decrease of nociceptive signals. Mechanisms of Nociceptive Signal Coding: Role of Slow Sodium Channels