Functional Role of Piezo1 Channels in Smooth Muscle Cells of Rat Cerebral Arteries under Normal Conditions and Chronic Carotid Artery Stenosis

In arterial smooth muscle cells, Piezo1 channels are involved in the regulation of vascular tone and remodeling in various diseases. They are non-selective cation channels, the activation of which can lead to depolarization of the smooth muscle cell membrane, Ca2+ entry through voltage-gated channels and the development of contraction. This work tested the hypothesis that Piezo1 channels are involved in regulating the tone of smooth muscle cells in small cerebral arteries, and functional contribution of these channels may change in chronic carotid artery stenosis. Constricting clips were placed on both common carotid arteries in rats (reducing the volume velocity of blood flow by at least 70%). After 4 weeks, the middle cerebral artery (MCA) was isolated for wire myography (after endothelial removal) and quantitative PCR. The level of MCA basal tone was lower in the rats of the Stenosis group than in the control group; contractile responses to thromboxane A2 receptor agonist U46619 were not changed. Incubation with Dooku1 (Piezo1 blocker, 30 µM) led to decreases in basal tone level and contractile responses to U46619 in MCA of control rats but did not have such effects in MCA of the Stenosis group. The contents of Piezo1 and voltage-gated L-type Ca2+ channel (CaV1.2) mRNAs did not differ between the groups, whereas the mRNA content of voltage-gated Ca2+ channels of the T type (CaV3.1) was decreased in the MCA of the Stenosis group compared to the control. Thus, Piezo1 channels have a pro-contractile effect in the smooth muscle cells of rat cerebral arteries, and this effect decreases with chronic stenosis of carotid artery. The decrease in the pro-contractile effect of Piezo1 in the MCA of rats of the Stenosis group may be associated with the development of changes not at the level of the Piezo1 channels themselves, but at subsequent stages of signal transduction to the contractile apparatus of smooth muscle cells.