Activation of intestinal smooth muscle cells by interstitial cells of Cajal in simulation studies

Abstract

Activation of a two-dimensional sheet network (5 parallel chains of 5 cells each) of simulated intestinal smooth muscle cells (SMCs) by one interstitial cell of Cajal (ICC) was modeled by PSpice simulation. The network of 25 cells was not interconnected by gap-junction channels; instead, excitation was transmitted by the electric field that develops in the junctional clefts (JC) when the prejunctional membrane fires an action potential (AP). Transverse propagation between the parallel chains occurs similarly. The ICC cell was connected to cell E5 of the network [5th cell of the 5th (E) chain] via a high-resistance junction. The stimulating current, applied to the ICC cell interior, was made to resemble the endogenous undershooting slow wave (I(SW)). An I(SW) of 2.4 nA (over a rise time of 4 ms) took the ICC cell from a resting potential (RP) of -80 mV to a membrane potential of -41 mV. The slow wave produced a large negative cleft potential in the JC (V(JC); ICC-E5). The V(jc) brought the postjunctional membrane of E5 to threshold, causing this cell to fire an AP. This, in turn, propagated throughout the SMC network. If the ICC cell was given an RP of -55 mV (like SMC) and a slow wave of 40 mV amplitude (I(SW) of 1.8 nA), it still activated the SMC network. This was also true when the ICC cell was made excitable (developing an overshooting, fast-rising AP). In summary, one ICC cell displaying a slow wave was capable of activating a network of SMC in the absence of gap junctions.