title: Exercise Prevents Upregulation of RyRs-BKCa Coupling in Cerebral Arterial Smooth Muscle Cells From Spontaneously Hypertensive Rats.
abstract: Regular exercise is an effective nonpharmacological means of preventing and controlling hypertension. However, the molecular mechanisms underlying its effects remain undetermined. The hypothesis that hypertension increases the functional coupling of large-conductance Ca(2+)-activated K(+) (BKCa) channels with ryanodine receptors in spontaneously hypertensive rats (SHR) as a compensatory response to an increase in intracellular Ca(2+) concentration in cerebral artery smooth muscle cells was assessed here. It was further hypothesized that exercise training would prevent this increase in functional coupling.
  
  
  
  SHR and Wistar-Kyoto (WKY) rats were randomly assigned to sedentary groups (SHR-SED and WKY-SED) and exercise training groups (SHR-EX and WKY-EX). Cerebral artery smooth muscle cells displayed spontaneous transient outward currents at membrane potentials more positive than -40 mV. The amplitude of spontaneous transient outward currents together with the spontaneous Ca(2+) sparks in isolated cerebral artery smooth muscle cells was significantly higher in SHR-SED than in WKY-SED. Moreover, hypertension displayed increased whole-cell BKCa, voltage-gated Ca(2+) channel, but decreased KV currents in cerebral artery smooth muscle cells. In SHRs, the activity of the single BKCa channel increased markedly, and the protein expression of BKCa (β1, but not α-subunit) also increased, but KV1.2 decreased significantly. Exercise training ameliorated all of these functional and molecular alterations in hypertensive rats.
  
  
  
  These data indicate that hypertension leads to enhanced functional coupling of ryanodine receptors-BKCa to buffer pressure-induced constriction of cerebral arteries, which attributes not only to an upregulation of BKCa β1-subunit function but also to an increase of Ca(2+) release from ryanodine receptors. However, regular aerobic exercise efficiently prevents augmented coupling and so alleviates the pathological compensation and restores cerebral arterial function.
authors.affiliation: From the Department of Exercise Physiology, Beijing Sport University, Beijing, P.R. China. l_j_shi72@163.com.
authors.forename: Lijun
authors.initials: L
authors.lastname: Shi
authors.affiliation: From the Department of Exercise Physiology, Beijing Sport University, Beijing, P.R. China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: From the Department of Exercise Physiology, Beijing Sport University, Beijing, P.R. China.
authors.forename: Yujia
authors.initials: Y
authors.lastname: Liu
authors.affiliation: From the Department of Exercise Physiology, Beijing Sport University, Beijing, P.R. China.
authors.forename: Boya
authors.initials: B
authors.lastname: Gu
authors.affiliation: From the Department of Exercise Physiology, Beijing Sport University, Beijing, P.R. China.
authors.forename: Run
authors.initials: R
authors.lastname: Cao
authors.affiliation: From the Department of Exercise Physiology, Beijing Sport University, Beijing, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: From the Department of Exercise Physiology, Beijing Sport University, Beijing, P.R. China.
authors.forename: Tengteng
authors.initials: T
authors.lastname: Zhao
mesh_terms: D000818:Animals; D001794:Blood Pressure; D020013:Calcium Signaling; D002536:Cerebral Arteries / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D005081:Exercise Therapy; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D051663:Kv1.2 Potassium Channel / Q000378:metabolism; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits / Q000378:metabolism*; D008564:Membrane Potentials; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000503:physiopathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020239:Receptor Cross-Talk; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D015398:Signal Transduction; D015854:Up-Regulation; D014661:Vasoconstriction
chemical_list: C496972:Kcna2 protein, rat; D051663:Kv1.2 Potassium Channel; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits; D019837:Ryanodine Receptor Calcium Release Channel
keywords: constriction; exercise; hypertension; potassium channel; rats