Urinary incontinence is associated with enhanced spontaneous phasic contractions of the detrusor smooth muscle (DSM). Although a complete understanding of the etiology of these spontaneous contractions is not yet established, it is suggested that the spontaneously evoked action potentials (sAPs) in DSM cells initiate and modulate the contractions. In order to further our understanding of the ionic mechanisms underlying sAP generation, we present here a biophysically detailed computational model of a single DSM cell. First, we constructed mathematical models for nine ion channels found in DSM cells based on published experimental data: two voltage-gated Ca2+ ion channels, an hyperpolarization-activated ion channel, two voltage-gated K+ ion channels, three Ca2+-activated K+ ion channels and a non-specific background leak ion channel. Incorporating these channels, our DSM model is capable of reproducing experimentally recorded spike-type sAPs of varying configurations, ranging from sAPs displaying after-hyperpolarizations to sAPs displaying after-depolarizations. Our model, constrained heavily by physiological data, provides a powerful tool to investigate the ionic mechanisms underlying the genesis of DSM electrical activity, which can further shed light on certain aspects of urinary bladder function and dysfunction.
Fig 10A of the paper. Following a synaptic input, our model, in its default setting, is able to generate spike type action potential with an after depolarization riding on the repolarization phase. The conductance, rising phase and falling phase time constants for the synaptic conductance (see Exp2Syn) are set to 0.0095 μS, 15 ms, and 25 ms respectively.
Reference: 1 . Mahapatra C, Brain KL, Manchanda R (2018) A biophysically constrained computational model of the action potential of mouse urinary bladder smooth muscle PLOS One, accepted