Excitability Characteristics of a Urinary Bladder Detrusor Smooth Muscle Cell as a Basis for Choosing Parameters of Rehabilitation Electrostimulation: A Simulation Study

Abstract

Electrical stimulation targeted at smooth muscle cells (SMCs) of the urinary bladder detrusor (UBD) is used in a complex of rehabilitation procedures performed during treatment of neurourological diseases, in particular of those associated with the deficiency of М2/М3 acetylcholine receptors modifying the efficacy of parasympathetic innervation of these cells. The choice of parameters of such stimulation meets difficulties because of limited knowledge about biophysical and physiological processes induced in the stimulated cells. Certain information about such processes can be obtained with the use of a UBD SMC computer model built according to the data of biological experiments characterizing ion channels, ion exchangers, and other mechanisms regulating the intracellular calcium concentration ([Ca2+] i ) typical of the prototype. We explored the standard characteristics of the electrical excitability of the model SMC (“strength – duration” relationship for the threshold current and dynamics of the refractoriness following generation of action potentials, APs), as well as coupled changes in the membrane potential, partial transmembrane currents, and [Ca2+] i values evoked by depolarizing current pulses. In some computational experiments, such stimulation was performed under conditions of a higher conductivity of purinergic ionotropic receptor channels, thereby mimicking the action of purinomimetics. The model UBD SMC generated APs with parameters close to those of the prototype; AP generation was accompanied by long periods of absolute and relative refractoriness (up to 30 and 600 msec, respectively). The relative refractoriness period included an early phase (AP half-recovery lasting about 220 msec) and a late phase; each of these phases included “fast” and “slow” components with the time constants differing from each other by an order of magnitude. These time characteristics of the refractoriness were determined by the kinetic characteristics of the processes of activation/inactivation of voltage- and calcium-dependent ion channels and by those of the [Ca2+] i return to the basal level under the action of a set of Са2+ extrusion mechanisms. An important UBD SMC biophysical parameter was also the reversal potential (E Cl) for calcium-dependent chloride current (which is activated, in particular, due to the parasympathetic action on М2/М3 receptors). This current changed its main “depolarizing” direction to the hyperpolarizing one when the membrane potential exceeded the E Cl level.