Electrophysiological modelling of pulmonary artery smooth muscle cells in the rabbits--special consideration to the generation of hypoxic pulmonary vasoconstriction.

In vascular smooth muscle cells, it has been suggested that membrane potential is an important component that initiates contraction. We developed a mathematical model to elucidate the quantitative contributions of major ion currents [a voltage-gated L-type Ca2+ current (ICaL), a voltage-sensitive K+ current (IKV), a Ca2+-activated K+ current (IKCa) and a nonselective cation current (INSC)] to membrane potential. In order to typify the diverse nature of pulmonary artery smooth muscle cells (PASMCs), we introduced parameters that are not fixed (variable parameters). The population of cells with different parameters was constructed and the cells that have the electrophysiological properties of PASMCs were selected. The contributions of each membrane current were investigated by sensitivity analysis and modification of the current parameters. Consequently, IKV and INSC were found to be the most important currents that affect the membrane potential. The occurrence of depolarisation in hypoxic pulmonary vasoconstriction (HPV) was also examined. In hypoxia, IKV and IKCa were reduced, but the consequent depolarisation in simulation was not enough to initiate contractions. If we add an increase of INSC (2.5-fold), the calculated membrane potential was enough to induce contraction. From the results, we conclude that the balance of various ion channel activities determines the resting membrane potential of PASMCs and our model was successful in explaining the depolarisation in HPV. Therefore, this model can be a powerful tool to investigate the various electrical properties of PASMCs in both normal and pathological conditions.

Differential distribution of mechanosensitive nonselective cation channels in systemic and pulmonary arterial myocytes of rabbits.

The mechanosensitive nonselective cation channel (NSC(MS)) is a key player in vascular myogenic contraction. The functional channel density and pressure sensitivity of NSC(MS) in vascular myocytes were compared between pulmonary and systemic arteries (coronary, mesenteric and cerebral arteries) in the rabbit. In cell-attached condition, a negative pressure via patch pipettes commonly activated NSC(MS) with weak voltage dependence. The threshold pressure for activation was lower, and the density of NSC(MS) was higher in the pulmonary than the systemic arteries. When the pulmonary arteries were divided into small-diameter (outer diameter, OD < 0.5 mm) and large-diameter (OD > 1.5 mm) arteries, the low threshold and high density of NSC(MS) were observed only in small-diameter ones. No such difference was observed between the small- and large-diameter coronary arteries. The higher stretch sensitivity and denser functional expression of NSC(MS) in small pulmonary arteries might suggest an adaptive tuning for the relatively low pulmonary blood pressure in vivo.