[Role of serine/threonine and tyrosine protein phosphatases in command Helix lucorum neurons at the cellular correlate of habituation].

Effects of some inhibitors of serine/threonine and tyrosine protein phosphatases on the depression and spontaneous recovery of the acetylcholine-induced inward current (ACh-current) in command Helix neurons of defensive behavior at the cellular correlate of habituation were investigated. The following drugs were used: okadaic acid (reduces activity ofphosphatases PP1 and PP2A), endothall (PP2A), cyclosporine A and cypermethrin (PP2B), CCT007093 (PPM1D), dephostatin (blocks tyrosine phosphatases). All used inhibitors modify the depression flow, and endothall reduces spontaneous recovery of ACh-current also.

[Role of myosins in depression of sensitivity of Helix neurons to acetylcholine in a cellular analog of habituation].

We investigated the involvement of cytoskeleton motor proteins, myosins, in the molecular mechanism of sensitivity depression to acetylcholine in Helix command neurons of defensive behavior in a cellular analog of habituation. There were analyzed the effects of several drugs disturbing myosin function: ML-7 and MLCK-IP-18--blockers of myosin light chain kinase, blebbistatin--an inhibitor of non-muscle myosin II, Y-27632--inhibitor of kinases ROCK-I and ROCK-II (activate mainly non-muscle myosin II) on the depression of acetylcholine-induced inward current. It was found that ML-7 and MLCK-IP- 18 weakened current depression; blebbistatin and Y-27632 did not change the depression.

[Role of actin microfilaments in depression of acetylcholine-induced current in Helix lucorum neurons on cellular analogue of habituation].

Toxins that impair the function of actin microfilaments in cytoskeleton, cytochalasin B (disrupts microfilaments by inhibiting actin polymerization) and phalloidin (binds polymeric F-actin, stabilizing it and interfering with the function of actin-rich structures) reduce the depression of acetylcholine-induced inward current in Helix lucorum command neurons of defensive behavior during rhythmical local acetylcholine applications to soma (cellular analogue of habituation). These results and mathematical simulation allow us to suggest that the depression of cholinosensitivity of extrasynaptic membrane zones in command neurons on the cellular analogue of habituation is associated with the involvement of actin microfilaments in reduction of the number of membrane cholinoreceptors.

[The role of serine/threonine and tyrosine protein kinases in the depression of cholinosensitivity in Helix lucorum neurons in the cellular correlate of habituation].

Inhibitor ofadenylate cyclase (SQ 22,536) and inhibitors ofserin/threonine protein kinases A (PKA -Rp-cAMPS), G (PKG - H-Arg-Lys-Arg-Ala-Arg-Lys-Glu-OH), calcium/calmodulin-dependent kinase II (CaMKII - KN-93), p38mitogen-activated (MAPK - PD 169316), and tyrosine protein kinases (genistein), including their Src-family (PP2), weaken the depression of the acetylcholine-induced inward current (ACh-current) in command Helix neurons of defensive behavior under conditions of rhythmical local acetylcholine applications to the soma in the cellular analogue of habituation. Selective inhibitor of protein kinase C (PKC - chelerythrine) does not change the depression of the ACh-current. Mathematical simulation of the influence of the inhibitors applied on a number of membrane-connected acetylcholine receptors made it possible to obtain the design curves consistent with the experimental curves of the ACh-current depression.

[Endocytosis of cholinoreceptors in the mechanism of depression of cholinosensitivity in Helix lucorum neurons in a cellular model of habituation].

Inhibitors of dynamin-dependent endocytosis (dynamin inhibitory peptide and dynasore) and inhibitors of tubulin (colchicine and vinblastine) decrease the depression of acetylcholine-induced inward current in command neurons of Helix defensive behavior under conditions of rhythmical local applications of acetylcholine to a neuron soma in a cellular model of habituation. Mathematical model which allows for the possibility of different localizations of receptors in a neuron and characteristics of receptor travel makes it possible to analyze the dependence of the current depression on some intracellular processes. We suggest that the cholinosensitivity depression of extrasynaptic membrane zones in command neurons of Helix defensive behavior in the cellular model of habituation under study is associated with dynamin-dependent endocytosis of cholinoreceptors with involvement of cytoskeleton microtubules.