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Korogod S.M.,Ukrainian Academy of Sciences | Demianenko L.E.,Dnipropetrovsk Medical Academy of the Ministry of Public Health of Ukraine
Neurophysiology | Year: 2017

Therapeutic neuroprotective hypothermia is becoming increasingly used to suppress abnormally high neuronal activity in the brain occurring under conditions of ischemic and traumatic injuries, refractory epilepsy, etc. This makes especially topical examination of the factors determining the temperature dependence of the intensity of neuronal excitation. In this respect, of interest are thermosensitive TRP-type channels conducting depolarization currents and found in central neurons. We explored such channels and their functional role using computer modeling. These channels were present in the membrane of a simulated dentate gyrus granule cell of the hippocampus. The chanels can be in two states, open and closed, and the probabilities of these states are temperature-dependent. The model adequately reproduced the key feature of the prototype, namely voltage-dependent activation of TRP channels shifted toward depolarization with a decrease in the temperature. At identical potentials, the level of such activation was reduced, i.e., a deactivation phenomenon was observed. The decrease of temperature from 37°C (normothermia) to 20°C (focal deep hypothermia) was accompanied by a significant decrease in the frequency of action potentials generated by the simulated neuron in response to tonic synaptic excitation of the same intensity. This hypothermic inhibition was most pronounced within the temperature range where temperature-dependent deactivation of TRP channels developed. This effect was much less manifested in the case where TRP channels were “turned off,” which mimicked their genetic knockout. Such results obtained on a rather simplified model reveal new aspects of the neuroprotective effect of hypothermia, which deserves further in-depth studies. © 2017 Springer Science+Business Media New York

Kochenov A.V.,Ukrainian Academy of Sciences | Kochenov A.V.,Dnipropetrovsk Medical Academy of the Ministry of Public Health of Ukraine | Poddubnaya E.P.,Dnipropetrovsk Medical Academy of the Ministry of Public Health of Ukraine | Korogod S.M.,Ukrainian Academy of Sciences
Neurophysiology | Year: 2016

In a computer model of an urinary bladder detrusor (UBD) smooth muscle cell (SMC), we investigated coupled changes in the membrane potential (MP), partial transmembrane currents, and intracellular calcium concentration ([Ca2 +]i), caused by parasympathetic stimulation. The respective data should help to determine the biophysical basis for the choice of parameters of medical rehabilitation electrical stimulation of the UBD. Ionotropic and metabotropic effects of such stimulation having different latency periods (LPs) were simulated by, respectively, an increase in the conductivity of purinoreceptor channels of the sarcolemma and a delayed (by 70 msec) increase in the permeability of calcium channels of the sarcoplasmic reticulum (store) sensitive to inositol triphosphate (IP3), the end-product of a chain of reactions triggered by activation of muscarinic cholinergic receptors. The modeled SMC responded to single stimulation by generation of action potential (AP) close in its parameters to those in the prototype. Application of long series of identical stimuli caused, after a transient interval, forced stationary oscillations of the MP and [Ca2 +]i. The magnitudes of the latter decreased, and the mean level increased with shortening of the interstimulus intervals (ISIs). It was found that the stimulation outcome needing prior experimental refining was determined by such parameters of the parasympathetic action as the durations of the purine and muscarinic components and the delay between these components. It has been shown that, during stimulation with ISIs shorter than the above-mentioned delay, the subsiquent stimulus activates P2X channels before expiration of the delay of the IP3-channel activation evoked by the preceding stimulus. This is actually equivalent to shortening of the interval between successive activations of P2X- and IP3-channels. Simple quantitative expressions were obtained for the parameters of stimulation; a given difference in the LPs of purine and muscarinic effects of parasympathetic stimulation allowed us to calculate the ISIs providing more efficient rehabilitation stimulation of the UBD parasympathetic nerves. © 2016 Springer Science+Business Media New York

Kochenov .V.,Ukrainian Academy of Sciences | Kochenov .V.,Dnipropetrovsk Medical Academy of the Ministry of Public Health of Ukraine | Poddubnaya E.P.,Dnipropetrovsk Medical Academy of the Ministry of Public Health of Ukraine | Korogod S..,Ukrainian Academy of Sciences
Neurophysiology | Year: 2015

The work was aimed at the search for approaches to solving the problem of biophysically reasonable selection of the parameters of electrical stimulation of smooth muscle cells (SMCs) of the urinary bladder detrusor (UBD). Such stimulation is widely used in the rehabilitation of patients with surgical correction of congenital malformations accompanied by total or partial deficiency of the M2/M3 cholinergic receptors in the UBD. A computer model built on the basis of experimental data on ion channels and pumps of the sarcolemma and mechanisms of regulation of the intracellular calcium concentration ([Ca22+]i), providing both electrogenesis and the contractile function of the cell inherent to the biological prototype, was used. We studied changes in the membrane potential, partial transmembrane currents, and [Ca2+]i, caused by depolarizing current pulses applied with constant frequencies and combined in “packs” or “envelopes” typical of the protocols of rehabilitation stimulation; the stimuli had constant or trapezoid-modulated amplitudes. The examined UBD SMC responded to a single pulse by generation of the action potential (AP) close in its properties to the prototype. Stimulation by both packs and envelopes of identical pulses eventually led to the establishing of equal forced electrical and concentration oscillations with the parameters depending on the duration of interpulse intervals (IPIs). Such oscillations caused by stimulation with 5- and 50-msec-long IPIs, typical of the rehabilitation protocols and comparable with the durations of the absolute and relative refractoriness of the model SMC, significantly differed in the pattern of the regenerative responses (APs) and in the range and mean levels of depolarization shifts of the membrane potential and those of [Ca2+]i, which were greater at high-frequency stimulation. In the case of short IPIs, [Ca2+]i, having no time to return to the basal level, oscillated within a range of values which in other excitable cells are considered to exceed significantly the physiological norm. These data emphasize the necessity to estimate the exact kinetic characteristics of the mechanisms underlying the inflow and extrusion of Ca2+ in the UBD SMC necessary for a biophysically justified choice of the parameters of rehabilitation stimulation that would prevent possible cytotoxic side effects associated with excessively long-lasting high levels of [Ca2+]i. Essential for the observed processes and, therefore, requiring targeted studies, was such a parameter of UBD SMCs as the reversal potential for Ca2+-dependent chloride current (ECl); this current is activated, in particular, by parasympathetic action on the M2/M3 receptors. When high-frequency oscillations of the membrane potential periodically exceeded the ECl level, the mentioned current changed its main (depolarizing) direction to the opposite (hyperpolarizing) one. © 2015, Springer Science+Business Media New York.

Rodinskii A.G.,Dnipropetrovsk Medical Academy of the Ministry of Public Health of Ukraine | Serdyuchenko I.Ya.,Dnipropetrovsk Medical Academy of the Ministry of Public Health of Ukraine | Demchenko T.V.,Dnipropetrovsk Medical Academy of the Ministry of Public Health of Ukraine
Neurophysiology | Year: 2013

In acute experiments on rats, we examined the effects of course systemic introduction of sodium gammahydroxybutyrate (NaGHB, 100 mg/kg, i.p., daily within 3 weeks) on consequences of compression of the right sciatic nerve, SN. In the control group, the nerve was compressed, but NaGHB was not injected. Electrical and force responses of the m. gastrocnemius+soleus (GS) and m. tibialis anterior (TA) evoked by stimulation of the n. tibialis comm. and n. peroneus comm., respectively, at the side of SN impairment and the opposite intact side were recorded. Compression of the SN induced in animals of the control group (with no injections of NaGHB) considerable increases in the values of the threshold and chronaxia of the stimulated nerve, decreases in the amplitude of EMG responses of the muscles, increases in the latencies of these reactions, and also decreases in the force responses developed at single and tetanic isometric contractions of the above muscles. At the side of SN compression, graphs of recovery of the second muscle response under conditions of paired stimulation of the nerves were shifted toward greater interstimulus intervals. Course introduction of NaGHB resulted in more than a twofold increase in the thresholds upon stimulation of the nerves; at the same time, the chronaxia values decreased. The amplitudes of EMG responses of the muscles after NaGHB injections became smaller than in the control, and the latencies of these responses increased. Under these conditions, curves of recovery of the second response at paired stimulation were shifted toward shorter interstimulus intervals. Introduction of NaGHB provided noticeable increases in the force responses of the tested muscles. Such changes were observed bilaterally, and the relative intensities of the corresponding modifications at the side of SN compression and the intact side were close to each other. Possible mechanisms of the effect of NaGHB on the state of the nerve/muscle apparatus of the limb after compression of a large nerve trunk resulting in the development of traumatic neuropathy are discussed. © 2013 Springer Science+Business Media New York.

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