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.
Model Type: Neuron or other electrically excitable cell
Currents: ATP-senstive potassium current; I Calcium; I h; I K,Ca; I K; I L high threshold; I T low threshold; IK Bkca; IK Skca
Model Concept(s): Action Potentials; Action Potential Initiation; Calcium dynamics; Ion Channel Kinetics
Simulation Environment: NEURON
References:
Mahapatra C, Brain KL, Manchanda R. (2018). A biophysically constrained computational model of the action potential of mouse urinary bladder smooth muscle. PloS one. 13 [PubMed]