Kochenov A. The excitability of the smooth muscle cells: influence of the ratio of ionotropic and metabotropic mechanisms (a simulation study)

This study is devoted to revealing the role played by the ratio of ionotropic and metabotropic mechanisms underlying the excitability of a smooth muscle cell of the urinary bladder detrusor (SMC UBD). For the first time, a model of the SMC UBD has been developed. It included a set of channels typical of a prototype. The SMC UBD model also includes an author's model of the Ca2+-dependent chloride current. The model adequately reproduces available experimental data (value of the resting membrane potential, amplitude of the action potential, shape and components of the action potential, including afterdepolarization and afterhyperpolarization, level of intracellular Ca2+ concentration at rest, level of intracellular Ca2+ concentration during its release from the intracellular store at modeling parasympathetic activity and the ratio of Ca2+-currents at the peak of action potential) obtained from cell's of the prototype, which means suitability of the model for the study of previously unstudied processes in this type of cells. It is shown that the value of the SMC UDB response to the action of parasympathetic stimulus is characteristically dependent upon the intensity ratio of ionotropic and metabotropic components of such stimulus. Currents through Ca2+-dependent chloride channels, which are the final element of the metabotropic signaling pathway, largely determine parasympathetic excitation of SMC UBD. Analysis of the excitability of the cell show that the complex, two-phase process of restoring the action potential amplitude is associated with the inactivation of calcium channels, decrease of their driving potential and kinetic parameters of the mechanisms of Ca2+ extrusion. We also found a reduction of the excitation threshold with increasing conductivity of the Р2Х receptor channels that mimics the action of purinomimetics. According to the impact of the ratio of metabotropic and ionotropic components of parasympathetic action on the excitability of an urinary bladder SMC, we observe the possibility of compensating for the weakened response of a cell to a parasympathetic stimulus caused by deficiency of the metabotropic muscarinic M2/M3-cholinoreceptors, by stimulation of the ionotropic Р2Х receptor channels. These results allow us to propose ways of optimization existing stimulation protocols, which are used in rehabilitation of the patients with diseases of lower urinary tract.