Sequential opening of IP3-sensitive Ca2+channels and SOC during α-adrenergic activation of rabbit vena cava
α1-Aderenoceptor-mediated constriction of rabbit inferior vena cava (IVC) is signaled by asynchronous wavelike Ca2+ 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 (InsP3)-sensitive Ca2+ release channels (IP3R channels) can prevent the initiation and abolish ongoing α1-aderenoceptor-mediated tonic constriction of the venous smooth muscle by inhibiting the generation of these intracellular Ca2+ concentration ([Ca2+]i) oscillations. The observed effects of 2-APB can only be attributed to its selective inhibition on the IP3R channels, not to its slight inhibition of the L-type voltage-gated Ca2+ channel and the sarco(endo)plasmic reticulum Ca2+ ATPase. Furthermore, 2-APB had no effect on the ryanodine-sensitive Ca2+ 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 IP3R-channel-mediated SR Ca2+ release or store depletion. This is in accordance with its sensitivity to Ni2+ and La3+ (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 IP3R channels and the SOC are required for PE-mediated [Ca2+]i oscillations and constriction of the rabbit IVC.