In‐Silico Investigation of Castration on Vas Deferens Smooth Muscle Electrophysiology

Abstract

OBJECTIVEThe vas deferens smooth muscle (VDSM) generates spontaneous contractions for the sperm transportation. The underlying electrical activities of the VDSM cell are prominently correlated with these contractions. According to a recent experimental study, the castration has down regulated the A‐type K+channel activities in the VDSM cell. However, the modulating properties of castration into VDSM electrophysiology are not investigated yet. In the present time, the in‐silico study plays a key role in understanding various complex physiological systems. To explore the quantitative contribution of castration to the VDSM membrane action potential (AP), a biophysically detailed single VDSM in‐silico cell model is simulated.METHODSThe in‐silico guinea‐pig VDSM cell model is constructed after incorporating a voltage‐gated Na+ ion channel, two voltage‐gated Ca2+ ion channels, a hyperpolarization‐activated ion channel, two voltage‐gated K+ ion channels, a Ca2+‐activated K+ ion channel, and a nonspecific background leak ion channel. All ion channel models are validated by comparing the simulated currents and current‐voltage relationship with those reported in the experimental studies. The modulating properties of the castration are simulated by mimicking the A‐type K+ channel on VDSM cell excitability.RESULTSThe ion channel conductnaces are set to maintain the resting membrane potential (RMP) at ̶ 50 mV as the physiological range of RMP in VDSM cell varies from ̶ 45 mV to ̶ 70 mV (Figure 1). The AP and membrane depolarization are generated in the whole cell model by applying an external current stimulus (10‐30 pA), as a brief square pulse of 10 ms duration. The A‐type K+ current is elicited by a 1000 ms depolarizing‐voltage‐step between ̶ 70 and +40 mV from a holding potential (̶ 80 mV) with 10 mV increments. The maximum conductance of A‐type K+ channel is altered to observe the changes in VDSM AP. The RMP, AP width, and AP peak are elevated by 2 mV, 15 ms, and 1 mV respectively after the castration (Figure 1). It reveals that the VDSM cell is more electrically excited due to the castration.CONCLUSIONSThe present in‐silico model, constrained heavily by physiological data, provides a powerful tool to investigate the ionic mechanisms underlying the genesis of VDSM electrical activity. In the guinea‐pig, following castration, the VDSM cell is excited by membrane depolarization, which causes to evoke more spontaneous contractions. The new biological insight from this investigation shows the agonist of the A‐type K+ channel might control the much‐diminished sex drive experiences for men after the castration.