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Abstract: TH-PO766

In Silico Pharmacological Assessment of Nifedipine and Mibefradil in Modulating Action Potential in Guinea Pig Ureter Smooth Muscle Cells

Session Information

  • Bioengineering
    October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Bioengineering

  • 300 Bioengineering


  • Mahapatra, Chitaranjan, Indian Institute of Technology Bombay, Mumbai, India

Urinary stones with higher diameter are unlikely to pass in the ureter in most situations. Activation of muscarinic and adrenergic receptors increases the amplitude of ureter smooth muscle (USM) contractions. Understanding the drug effects with respect to various ion channels offers several possibilities for safety pharmacological assessment. Here our overarching objective is to utilize the computational model to simulate the effects of nifedipine and mibefradil on the USM cell action potential (AP).


The USM cell is described as an equivalent electrical circuit with a number of variable conductances representing two voltage-gated Ca2+ (T - type and L- type) channels, two voltage-gated potassium channels, three calcium-dependent potassium channels. A drug model for nifedipine and mibefradil were simulated by multiplying the maximal conductance of L-type and T-type Ca2+ channels with a scaling factor between 0 and 1 to mimic the drug concentration. The maximum conductance value of the L-type and T-type Ca2+ channels were set to 0.00006 and 0.00002 mho/cm2 respectively.


The resting membrane potential (RMP) was set at — 50mV . A current pulse of 2 nA for 50 ms was injected to evoke the AP. The peak amplitude of AP and total inward current were substantially reduced after adding nifedipine by 50% and 100 % of it's control value. Adding mibefradil by 50% of it's control value reduced the peak amplitude of AP and inward current. However, the addition of mibefradil by 100% resulted no AP and zero inward current. The results showed that both L-type and T-type Ca2+ channels play important roles in generating APs, although L-type calcium channel is the major contributor to the total inward current. This simulation showed that the activation of more T-type Ca2+ channels will cause higher excitability of the USM cell.


Our approach provides a “virtual workbench” for simulating USM cell AP with maximal objectivity and faithfulness with regard to recordings in experiments. This in silico assessment showed that while inhibition of L-type Ca2+ channel suppresses or eliminates APs, the RMP is left unaffected. Complete inhibition of T-type Ca2+ channel also reduced USM cell excitability. A compound of nifedipine and mibefradil may form a new pharmacological maneuver towards USM cell contraction of high amplitude.