Title

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

Document Type

Article

Publication Title

American Journal of Physiology - Heart and Circulatory Physiology

ISSN

0363-6135

Volume

282

Issue

5 51-5

DOI

10.1152/ajpheart.00637.2001

Publication Date

1-1-2002

Abstract

α -Aderenoceptor-mediated constriction of rabbit inferior vena cava (IVC) is signaled by asynchronous wavelike Ca 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 )-sensitive Ca release channels (IP R channels) can prevent the initiation and abolish ongoing α -aderenoceptor-mediated tonic constriction of the venous smooth muscle by inhibiting the generation of these intracellular Ca concentration ([Ca ] ) oscillations. The observed effects of 2-APB can only be attributed to its selective inhibition on the IP R channels, not to its slight inhibition of the L-type voltage-gated Ca channel and the sarco(endo)plasmic reticulum Ca ATPase. Furthermore, 2-APB had no effect on the ryanodine-sensitive Ca 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 R-channelmediated SR Ca release or store depletion. This is in accordance with its sensitivity to Ni and La (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 R channels and the SOC are required for PE-mediated [Ca ] oscillations and constriction of the rabbit IVC. 1 3 3 1 i 3 3 3 i 2+ 2+ 2+ 2+ 2+ 2+ 2+ 2+ 2+ 3+ 2+

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