title: Sequential opening of IP(3)-sensitive Ca(2+) channels and SOC during alpha-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.
authors.affiliation: The iCAPTURE Center, University of British Columbia, St. Paul's Hospital, Vancouver, British Columbia V6Z 1Y6, Canada.
authors.forename: Cheng-Han
authors.initials: CH
authors.lastname: Lee
authors.forename: Roshanak
authors.initials: R
authors.lastname: Rahimian
authors.forename: Tania
authors.initials: T
authors.lastname: Szado
authors.forename: Jasmin
authors.initials: J
authors.lastname: Sandhu
authors.forename: Damon
authors.initials: D
authors.lastname: Poburko
authors.forename: Tasniem
authors.initials: T
authors.lastname: Behra
authors.forename: Lally
authors.initials: L
authors.lastname: Chan
authors.forename: Cornelis
authors.initials: C
authors.lastname: van Breemen
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002213:Capsid / Q000037:antagonists & inhibitors / Q000502:physiology; D036022:Capsid Proteins; D005656:Fungal Proteins / Q000235:genetics; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology*; D015640:Ion Channel Gating / Q000502:physiology*; D007811:Lanthanum / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009532:Nickel / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014661:Vasoconstriction / Q000187:drug effects; D014682:Vena Cava, Inferior / Q000502:physiology*
chemical_list: D001896:Boron Compounds; D015220:Calcium Channels; D036022:Capsid Proteins; D005656:Fungal Proteins; D012333:RNA, Messenger; D011942:Receptors, Adrenergic, alpha; C103392:small outer capsid protein, bacteriophage T4; D007811:Lanthanum; D009532:Nickel; D015544:Inositol 1,4,5-Trisphosphate; C109986:2-aminoethoxydiphenyl borate