title: Myogenic contraction by modulation of voltage-dependent calcium currents in isolated rat cerebral arteries.
abstract: 1. Tissue blood flow and blood pressure are regulated by the spontaneous, myogenic, contraction developed by resistance arteries. However, the cellular mechanisms underlying myogenic contraction are not understood. In this study, the mechanisms of myogenic contraction in cerebral resistance arteries were investigated. 2. The vasoconstriction observed in response to increased pressure in cerebral resistance arteries (myogenic reactivity) was dependent on Ca2+ entry through voltage-dependent Ca2+ channels, since it was abolished by Ca2+ removal and by dihydropyridine antagonists of voltage-dependent Ca2+ channels. 3. Myogenic reactivity persisted in a high-K+ saline, with reduced Ca2+, where membrane potential is presumed to be clamped. Therefore, membrane depolarization alone does not fully account for the increased voltage-dependent Ca2+ channel opening. 4. Voltage-dependent Ca2+ currents in single smooth muscle cells isolated from the resistance artery were substantially increased by applying positive pressure to the patch electrode evoking membrane stretch. 5. Myogenic reactivity remained unaffected by ryanodine and therefore was independent of internal ryanodine-sensitive Ca2+ stores. 6. The myofilament Ca2+ sensitivity was not increased by elevated pressure in alpha-toxin-permeabilized arteries. However, pharmacological activation of protein kinase C or G proteins did increase the myofilament Ca2+ sensitivity. 7. Myogenic contraction over the pressure range 30-70 mmHg could be accounted for by an increase in [Ca2+]i from 100 to 200 nM. 8. It is concluded that modest increases in [Ca2+]i within the range 100-200 nM can account for that myogenic contraction, and that stretch-evoked modulation of Ca2+ currents may contribute to the myogenic response.
authors.affiliation: Division of Neuroscience and Biomedical Systems, University of Glasgow, UK. J.McCarron@biomed.gla.ac.uk
authors.forename: J G
authors.initials: JG
authors.lastname: McCarron
authors.forename: C A
authors.initials: CA
authors.lastname: Crichton
authors.forename: P D
authors.initials: PD
authors.lastname: Langton
authors.forename: A
authors.initials: A
authors.lastname: MacKenzie
authors.forename: G L
authors.initials: GL
authors.lastname: Smith
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002199:Capillary Permeability / Q000502:physiology; D002536:Cerebral Arteries / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004594:Electrophysiology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D010738:Type C Phospholipases / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology
chemical_list: D015220:Calcium Channels; D002614:Chelating Agents; D004533:Egtazic Acid; D011493:Protein Kinase C; D010738:Type C Phospholipases