Biophysical Mechanism of Parasympathetic Excitation of Urinary Bladder Smooth Muscle Cells: a Simulation Study

Using the Hodgkin-Huxley formalism, we developed a computer model of a smooth muscle cell (SMC) of the urinary bladder detrusor; the model included the main types of ion channels and pumps, as well as intracellular calcium regulatory mechanisms inherent in the prototype cell. The biophysical mechanisms of generation of action potentials (APs) necessary for initiation of muscle contraction and those of calcium transients in response to parasympathetic activation of metabotropic М2/М3-cholinoreceptors and co-activation of Р2Х-purinoreceptors were investigated. The simulated SMC in response to a depolarizing current pulse generated an AP that was, by a number of indices, similar to real APs and was also accompanied by a transient elevation of the intracellular calcium concentration. We demonstrated a possibility of generation of such APs in response to a transient increase in the conductivity of channels of calcium-dependent chloride current accompanied by increase in the conductivity of channels associated with Р2Х-receptors (the conductivity ratio was 95 to 5 % and similar to that in the prototype). For the AP generation, temporal relations of the processes of increases in the mentioned conductances simulating the final effect of activation of М2/М3- and Р2Х-receptors were significant. These results obtained on the rather simplified model allow researchers to use the latter as an appropriate starting point for the development of more detailed models (in particular, those representing cascades of metabolic reactions triggered by a parasympathetic action).