Biophysical Processes in a Urinary Bladder Detrusor Smooth Muscle Cell during Rehabilitation Stimulation of Parasympathetic Efferents: a Simulation Study

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.