Romanenko S. Calcium signaling specificity in the different types of primary nociceptive neurons and its modulation

These thesis is devoted to investigation of functioning features of TRPV1 channels, which are expressed in dorsal root ganglion neurons somas of small (25 mkm and less) and medium (35-25 mkm) sizes as well to their influence on free calcium intracellular concentration oscillations. All mentioned further calcium transients were measured with calcium sensitive fluorescent dye Fura 2/AM. The blockage of TRPV1 channels by capsazepine lead to the alteration in amplitude of calcium transient caused by depolarization of neuron's membrane. Transient amplitude decreases on the average on 21 % among neurons with a middle size somas, and on 17.5 % - for neurons with a small size somas as compared to respect control transients. The influence of antiepileptic drug gabapentin (25 mkM) on calcium transients caused by rat dorsal root ganglion neurons membranes' depolarization was investigated. Gabapentin treatment of large size neurons does not change any characteristic parameters in calcium transients. Calcium transients of medium size neurons indicate 27 % of decreasing in amplitude. In the case of small size neurons the calcium transient amplitude indicate 4% diminishing comparatively to control and does not have statistical significance. The application of gabapentin on the dorsal root ganglion neurons during activating of TRPV1 channels by capsaicin causes considerable changes in the calcium transient parameters values comparatively with control ones. Transient amplitude of the former was decreased on 50.4 %, duration - on 66.2 %, and semiduration - on 57.9 % in comparison with latter. Thus, gabapentin mediated influence on function of TRPV1 channels in somas of primary sensory neurons was shown. The effect of gabapentin on calcium transients caused by depolarization in the dorsal root ganglion neurons of rats under condition of streptozotocin induced diabetes was investigated.The result of diabetes development on duration of transients at the half of amplitude level was considerably less dramatic in comparison with full duration. Application of gabapentin resulted in diminishing of calcium transient's amplitude, as well its complete duration and semiduration. The most significant effect of gabapentin was observed for the large dorsal root ganglion neurons where calcium transient amplitude diminished on 36%, and general duration - more than three times. Application of gabapentin on sensory neurons with medium size somas of diabetic animals during activating of TRPV1 channels results in diminishing of transient's amplitude value on 16 % in relation to control. Most significant changes were observed for duration of the transient, in relation to a control value it was decreased on 28.7 %.