Presenting Author Indian Institute of Technology Bombay
Objective:
The 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.
Methods:
The 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.
Results:
The 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.
Conclusions:
The 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.
Figure 1 Modulating effects of castration on VDSM action potential
