Ryanodine-induced vasoconstriction of the gerbil spiral modiolar artery depends on the Ca2+sensitivity but not on Ca2+sparks or BK channels.
BACKGROUND
In many vascular smooth muscle cells (SMCs), ryanodine receptor-mediated Ca2+sparks activate large-conductance Ca2+-activated K+(BK) channels leading to lowered SMC [Ca2+]iand vasodilation. Here we investigated whether Ca2+sparks regulate SMC global [Ca2+]iand diameter in the spiral modiolar artery (SMA) by activating BK channels.


METHODS
SMAs were isolated from adult female gerbils, loaded with the Ca2+-sensitive flourescent dye fluo-4 and pressurized using a concentric double-pipette system. Ca2+signals and vascular diameter changes were recorded using a laser-scanning confocal imaging system. Effects of various pharmacological agents on Ca2+signals and vascular diameter were analyzed.


RESULTS
Ca2+sparks and waves were observed in pressurized SMAs. Inhibition of Ca2+sparks with ryanodine increased global Ca2+and constricted SMA at 40 cmH2O but inhibition of Ca2+sparks with tetracaine or inhibition of BK channels with iberiotoxin at 40 cmH2O did not produce a similar effect. The ryanodine-induced vasoconstriction observed at 40 cmH2O was abolished at 60 cmH2O, consistent with a greater Ca2+-sensitivity of constriction at 40 cmH2O than at 60 cmH2O. When the Ca2+-sensitivity of the SMA was increased by prior application of 1 nM endothelin-1, ryanodine induced a robust vasoconstriction at 60 cmH2O.


CONCLUSIONS
The results suggest that Ca2+sparks, while present, do not regulate vascular diameter in the SMA by activating BK channels and that the regulation of vascular diameter in the SMA is determined by the Ca2+-sensitivity of constriction.
Anatomy & Physiology Department, Cell Physiology Laboratory, Kansas State University, 228 Coles Hall, Manhattan, Kansas, 66506-5802, USA.
Gayathri
G
Krishnamoorthy
Anatomy & Physiology Department, Cell Physiology Laboratory, Kansas State University, 228 Coles Hall, Manhattan, Kansas, 66506-5802, USA.|Department of Otolaryngology-Head and Neck Surgery, Tübingen Hearing Research Centre, and Molecular Physiology of Hearing, University of Tübingen, Tübingen, Germany.
Katrin
K
Reimann
Anatomy & Physiology Department, Cell Physiology Laboratory, Kansas State University, 228 Coles Hall, Manhattan, Kansas, 66506-5802, USA. wange@vet.ksu.edu.
Philine
P
Wangemann
D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D003051:Cochlea / Q000098:blood supply* / Q000187:drug effects / Q000502:physiology*; D019332:Endothelin-1 / Q000008:administration & dosage; D005260:Female; D005849:Gerbillinae; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000098:blood supply / Q000187:drug effects / Q000502:physiology; D012433:Ryanodine / Q000008:administration & dosage*; D014661:Vasoconstriction / Q000187:drug effects
D019332:Endothelin-1; D051036:Large-Conductance Calcium-Activated Potassium Channels; D012433:Ryanodine
BK channels; Ca2+ sensitivity; Ca2+ spark; Ryanodine; Spiral modiolar artery; Tetracaine; Vascular diameter