A computational model of the [Formula: see text] transients and influence of buffering in guinea pig urinary bladder smooth muscle cells.

Abstract

Many cellular events including electrical activity and muscle contraction are regulated and coordinated by intracellular [Formula: see text] concentration ([[Formula: see text]][Formula: see text]. In detrusor smooth muscle (DSM) cells, [[Formula: see text]]i is normally maintained at very low levels and rises transiently during signalling processes as a result of (i) influx from the extracellular space (mainly via L-type and T-type [Formula: see text] channels) and (ii) [Formula: see text] release from sarcoplasmic reticulum (SR) into the cytoplasm. Intracellular [Formula: see text] buffers, both fixed and diffusible, play a vital role in shaping the radial distribution of free [Formula: see text]. Our aim, in the work presented here, is to develop a mathematical model of [Formula: see text] buffering and diffusion and to generate [Formula: see text] transient in guinea pig DSM cells. The [Formula: see text] transient is generated using inward [Formula: see text] current that arises following voltage clamp and mediated by L-type and T-type [Formula: see text] channels. [Formula: see text] transient is obtained for different radial locations (or shells) of the DSM cytosol. This modeling study explores the levels of [[Formula: see text]]i achieved near the plasma membrane and in deeper locations. The [Formula: see text] transient generated in our model shows a high degree of similarity with experimental findings in terms of amplitude, duration and half-decay time. A number of different buffer properties such as concentration and mobility are tested for their effect on amplitude and shape of [Formula: see text] transient. The presence of fast buffer concentration in the cytosol markedly delays the rise of [[Formula: see text]]i in the core of the cell. Increase in the mobility of fast buffer slightly speeds up the redistribution of [Formula: see text]. To explore the model further, the role of plasma membrane [Formula: see text]-ATPase (PMCA) pump, sarcoplasmic/endoplasmic reticulum [Formula: see text]-ATPase (SERCA) pump and sodium calcium exchanger (NCX) on [Formula: see text] transient is studied and it is suggested that NCX may be of primary importance for the immediate lowering of [[Formula: see text]]i during the falling phase of a [Formula: see text] transient in DSM cells.