title: Ca(2+) oscillations regulate contraction of intrapulmonary smooth muscle cells.
abstract: Pulmonary blood pressure is a function of the resistance of the intrapulmonary blood vessels. Consequently, the mechanisms controlling blood vessel smooth muscle cell (SMC) contraction serve as potential sites for hypertension therapy. To explore these mechanisms, access to the intrapulmonary vessels is required and this is provided by the observation of a unique lung slice preparation with microscopy. There are 2 major processes that determine SMC tone; the intracellular Ca(2+) concentration and the sensitivity of the SMCs to Ca(2+). Agonist-induced increases in Ca(2+) occur in the form of propagating Ca(2+) oscillations that predominately utilize internal Ca(2+) stores and inositol trisphosphate receptors. The frequency of these Ca(2+) oscillations correlates with contraction. Agonists also increase Ca(2+) sensitivity of SMCs to enhance contraction. Changes in membrane potential mediated by KCl also stimulate contraction via slow Ca(2+) oscillations and increased sensitivity. However, these slow Ca(2+) oscillations rely on Ca(2+) influx to drive the cyclic release of over-filled Ca(2+) stores via the ryanodine receptor. The relaxation of SMC tone can be induced by the reduction of the frequency of the Ca(2+) oscillations and the Ca(2+) sensitivity by b(2)-adrenergic agonists or nitric oxide.
authors.affiliation: Department of Physiology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA, 01655, USA. Michael.Sanderson@umassmed.edu
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Sanderson
authors.forename: Yan
authors.initials: Y
authors.lastname: Bai
authors.forename: Jose
authors.initials: J
authors.lastname: Perez-Zoghbi
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D006801:Humans; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D011651:Pulmonary Artery / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D011652:Pulmonary Circulation / Q000502:physiology; D011667:Pulmonary Veins / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; D012701:Serotonin; D011189:Potassium Chloride; D000109:Acetylcholine; D002118:Calcium