title: Reduction of Ca(2+) channel activity by hypoxia in human and porcine coronary myocytes.
abstract: OBJECTIVE
  Oxygen (O(2)) tension is a major regulator of blood flow in the coronary circulation. Hypoxia can produce vasodilation through activation of ATP regulated K(+) (K(ATP)) channels in the myocyte membrane, which leads to hyperpolarization and closure of voltage-gated Ca(2+) channels. However, there are other O(2)-sensitive mechanisms intrinsic to the vascular smooth muscle since hypoxia can relax vessels precontracted with high extracellular K(+), a condition that prevents hyperpolarization following opening of K(+) channels. The objective of the present study was to determine whether inhibition of Ca(2+) influx through voltage-dependent channels participates in the response of coronary myocytes to hypoxia.
  
  
  METHODS
  Experiments were performed on porcine anterior descendent coronary arterial rings and on enzymatically dispersed human and porcine myocytes of the same artery. Cytosolic [Ca(2+)] was measured by microfluorimetry and whole-cell currents were recorded with the patch clamp technique.
  
  
  RESULTS
  Hypoxia (O(2) tension approximately 20 mmHg) dilated endothelium-denuded porcine coronary arterial rings precontracted with high K(+) in the presence of glibenclamide (5 microM), a blocker of K(ATP) channels. In dispersed human and porcine myocytes, low O(2) tension decreased basal cytosolic [Ca(2+)] and transmembrane Ca(2+) influx independently of K(+) channel activation. In patch clamped cells, hypoxia reversibly inhibited L-type Ca(2+) channels. RT-PCR indicated that rHT is the predominant mRNA variant of the alpha(1C) Ca(2+) channel subunit in human coronary myocytes.
  
  
  CONCLUSIONS
  Our study demonstrates, for the first time in a human preparation, that voltage-gated Ca(2+)channels in coronary myocytes are under control of O(2) tension.
authors.affiliation: Laboratorio de Investigaciones Biomédicas, Edificio de Laboratorios, 2 planta, Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Avenida Manuel Siurot s/n, E-41013 Seville, Spain.
authors.forename: T
authors.initials: T
authors.lastname: Smani
authors.forename: A
authors.initials: A
authors.lastname: Hernández
authors.forename: J
authors.initials: J
authors.lastname: Ureña
authors.forename: A G
authors.initials: AG
authors.lastname: Castellano
authors.forename: A
authors.initials: A
authors.lastname: Franco-Obregón
authors.forename: A
authors.initials: A
authors.lastname: Ordoñez
authors.forename: J
authors.initials: J
authors.lastname: López-Barneo
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism*; D003331:Coronary Vessels; D003600:Cytosol / Q000378:metabolism; D005470:Fluorometry; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine; D014664:Vasodilation
chemical_list: D020746:Calcium Channels, L-Type; D026902:Potassium Channel Blockers; D012333:RNA, Messenger; D005905:Glyburide; D002118:Calcium