Proceedings of The Physiological Society

Physiology 2015 (Cardiff, UK) (2015) Proc Physiol Soc 34, C38

Oral Communications

A computational model of the ionic currents and action potentials underlying contraction of isolated urinary bladder smooth muscle

C. Mahapatra1, K. Brain2, R. Manchanda1

1. Bio science & Bio engineering, Indian Institute of Technology Bombay, Mumbai, Maharastra, India. 2. University of Birmingham, Birmingham, United Kingdom.

  • Figure 1. Experimental AP (Adapted from [4]) (A) and simulated AP (B) in DSM model

  • TABLE I Comparison between simulated AP and Experimental AP [4]<\#13>

Motivation: Urinary incontinence (UI) is the involuntary loss of urine that creates a social or hygiene problem. Among different types of UI, bladder over activity is one, which is an overactive detrusor smooth muscle (DSM). It is well known that electrophysiological phenomena generates spontaneous electrical activities that intern causes spontaneous contraction due to elevation of intracellular Ca2+ concentration [1,2]. In order to understand the ionic mechanisms which generate electrical activities such as action potentials (APs) and synaptic depolarizations, we aimed to establish a computational model of sufficient biophysical detail to simulate DSM APs which in turn can shed light on genesis of bladder over activity. Based on recent experimental evidence [3,4.5], we construct mathematical models for seven ionic currents of DSM, where the magnitudes and kinetics of each ionic current are described by differential equations, in terms of maximal conductances, electro chemical gradients, and voltage-dependent activation/inactivation gating variables. The model is validated step by step by comparing simulated AP with experimental AP adapted from literature [4]. Methods: The model of active ion channels are based on classical Hodgkin-Huxley approach in parallel conductance model. Membrane capacitance (Cm) is taken as 1µF/cm2. The membrane resistance (Rm) is 138MΩ- cm2 and axial resistance is 181Ω-cm. The time dependence of the membrane potential is governed by dVm/dt = ─ Iion(t)/Cm where Vm (in mV) represents the transmembrane potential, and Iion (in pA) represents the sum of the ionic currents crossing the cell membrane. Results: Active conductances for rising phase are a large voltage gated L type Ca2+ current and small T type Ca2+ current current .Similarly voltage gated K+ current and calcium gated K+ currents are present in falling phase of the spike. Figure 1 shows both simulated AP and experimental AP in same scale, where Table 1 presents the validation in terms of resting membrane potential (RMP), Peak , after hyperpolarization (AHP) and AP duration. The AP generated from simulation resembles the AP from experiment up to a great extent. The simulation result doesn't fully recreate the experimental AP. This may be absence of the medium conductance Ca2+ - activated K+ (IK) channel in our model. Conclusion: The model reproduces successfully the generation of single spike in DSM that fit with the experimental data.Future perspectives of this work consist in adding more active channels, Na+- Ca2+ exchanger, plasma membrane Ca2+ ATPase pump and sarcoplasmic reticulum Ca2+ ATPase pump for a more comprehensive model.

Where applicable, experiments conform with Society ethical requirements