Sequential opening of IP₃-sensitive Ca²⁺channels and SOC during α-adrenergic activation of rabbit vena cava

Abstract

Alpha(1)-aderenoceptor-mediated constriction of rabbit inferior vena cava (IVC) is signaled by asynchronous wavelike Ca(2+) oscillations in the in situ smooth muscle. We have shown previously that a putative nonselective cationic channel (NSCC) is required for these oscillations. In this report, we show that the application of 2-aminoethoxyphenyl borate (2-APB) to antagonize inositol 1,4,5-trisphosphate (InsP(3))-sensitive Ca(2+) release channels (IP(3)R channels) can prevent the initiation and abolish ongoing alpha(1)-aderenoceptor-mediated tonic constriction of the venous smooth muscle by inhibiting the generation of these intracellular Ca(2+) concentration ([Ca(2+)](i)) oscillations. The observed effects of 2-APB can only be attributed to its selective inhibition on the IP(3)R channels, not to its slight inhibition of the L-type voltage-gated Ca(2+) channel and the sarco(endo)plasmic reticulum Ca(2+) ATPase. Furthermore, 2-APB had no effect on the ryanodine-sensitive Ca(2+) release channel and the store-operated channel (SOC) in the IVC. These results indicate that the putative NSCC involved in refilling the sarcoplasmic reticulum (SR) and maintaining the tonic contraction is most likely an SOC-type channel because it appears to be activated by IP(3)R-channel-mediated SR Ca(2+) release or store depletion. This is in accordance with its sensitivity to Ni(2+) and La(3+) (SOC blockers). More interestingly, RT-PCR analysis indicates that transient receptor potential (Trp1) mRNA is strongly expressed in the rabbit IVC. The Trp1 gene is known to encode a component of the store-operated NSCC. These new data suggest that the activation of both the IP(3)R channels and the SOC are required for PE-mediated [Ca(2+)](i) oscillations and constriction of the rabbit IVC.

Ca2+ signaling in mouse mesenteric small arteries: myogenic tone and adrenergic vasoconstriction

“…The Ca 2ϩ signaling elicited by PE under this condition ( Fig. 4A; see "10PE_before_tone" movie in supplemental data) was similar to that we and others have reported previously for rat mesenteric small arteries (23,28,36), rabbit inferior vena cava (21,30), rat tail artery (1,8), and rat cerebral small artery (11). Briefly, upon exposure to PE (1-10 M), most vascular SMCs in the mouse mesenteric small arteries produced asynchronous propagating Ca 2ϩ waves, with the numbers of cells producing Ca 2ϩ waves and the frequency of the Ca 2ϩ waves being a function of the [PE] (Fig.…”

ATP-induced mitogenesis is mediated by cyclic AMP response element-binding protein-enhanced TRPC4 expression and activity in human pulmonary artery smooth muscle cells

“…TRPC gene products have been suggested as potential underlying components of native SOC in the cardiovascular system (16,39,43). TRPC1, TRPC4, and TRPC6 figure prominently as components of native SOC in pulmonary VSMC and endothelial cells and are involved in regulating vascular tone, microvascular permeability, and cell proliferation (5,13,17,21,33,40,61,62,68,70,72).…”

IP3 receptors regulate vascular smooth muscle contractility and hypertension

“…The latter binds to IP 3 Rs and causes Ca 2+ channels to open, which subsequently leads to Ca 2+ release from the ER and an increase in cytosolic Ca 2+ concentration, thereby resulting in cell contraction (16,17). To date, most studies describing IP 3 R regulation of vascular smooth muscle contractility involve the use of IP 3 R blockers (18)(19)(20).…”