Fedorenko A. Redox modulation ATP and proton gated channels in primary sensory neurons and pyramidal neurons of hippocampus

This dissertation is devoted to the investigation of action of endogenous and exogenic oxidants and antioxidants in the primary sensory neurones and pyramidal neurones of hippocampus. It was shown that in the presence of endogenous antioxidants proton gated currents is increased on 46-31% in the trigeminal, dorsal primary sensory neurones and in the pyramidal neurones of hippocampus. The oxidant DTNB reduced the amplitude of proton gated channels on 35%. It was found that fractional Ca2+ current of proton gated channels was increased disproportionately as compared with Na+ compound of proton gated channels, at the same time the kinetics of desensitisation of proton gated channels was slow down under antioxidants. It was analysed the influence of redox reagents on АТP gated channels in the nodosum sensory neurones. Inward current was increased on 110%, but the kinetics of inactivation and desensitisation did not occur any modifications. It is well known that ATP and proton gated channels are involved in the nociception. The big amount of glutathione is released from presynaptic slip and from astrocytes and the peripheral concentration of antioxidants is increased, thus under conditions of our experiments we can assume that acidosis causes hyperalgesia and sensitisation of ligand-gated channels of ganglion neurones investigated. Thus, during ischemia for example, signalisation of nociceptor receptors become stronger. ATP gated channels have high permeability to the Ca2+. Our results show that ATP-activated current is increased in the presence of glutatione, and in the same time the Ca2+ is increased too. Ca2+ is well known intracellular messenger, so that the increase of Ca2+ concentration may leads to big amount of cellular events, such as Ca2+ realising from intracellular calcium storage and apoptosis.