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논문분류	춘계학술대회 초록집
제목	In scilico pharmacological assessment of nifedipine and mibefradil in modulating action potential in guinea pig ureter smooth muscle cells.
저자	Chitaranjan Mahapatra, Rohit Manchanda
출판정보	2018; 2018(1):
키워드	ureter smooth muscle \| Urinary stones \| action potential \| voltage gated Ca2+ channel
초록	Objectives: Urinary stones with higher diameter are unlikely to pass in 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 additional 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). Methods: 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 Ca channel with a scaling factor between 0 and 1 to mimic the drug concentration. Results: The resting membrane potential (RMP) is set at ─50mV . A current pulse of 2 nA for 10 ms is injected to evoke the AP. The peak amplitude of AP and total inward current are substantially reduced after adding nifedipine by 50% and 100 % of its control value. Adding mibefradil by 50% of its control value reduced the peak amplitude of AP and inward current. However, the addition of mibefradil by 100% results no AP and zero inward currents. The results show that both L-type and T-type calcium channel play important roles in generating APs, although L-type calcium channel is the major contributor to the total inward current. Conclusions: This in silico assessment showed that while inhibition of L-type Ca channel suppresses or eliminates APs, the RMP is left unaffected. Complete inhibition of T-type Ca 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.
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