Ca2+ sparks and their function in human cerebral arteries.
OBJECTIVE
Local Ca2+ release events (Ca2+ sparks) caused by the opening of ryanodine-sensitive Ca2+ channels in the sarcoplasmic reticulum have been suggested to oppose constriction in cerebral arteries through the activation of large-conductance Ca2+-activated K+ (BK) channels. We report the first identification and characterization of Ca2+ sparks and associated BK channel currents in smooth muscle cells isolated from human cerebral arteries.


METHODS
Membrane currents and intracellular Ca2+ were measured with the use of the patch-clamp technique and laser scanning confocal microscopy.


RESULTS
Ca2+ sparks with a peak fractional fluorescence change (F/F0) of 2.02 +/- 0.04 and size of 8.2 +/- 0.5 microm2 (n=108) occurred at a frequency of approximately 1 Hz in freshly isolated, cerebral artery myocytes from humans. At a holding potential of -40 mV, the majority of, but not all, Ca2+ sparks (61 of 85 sparks) were associated with transient BK currents. Consistent with a role for Ca2+ sparks in the control of cerebral artery diameter, agents that block Ca2+ sparks (ryanodine) or BK channels (iberiotoxin) were found to contract human cerebral arteries.


CONCLUSIONS
This study provides evidence for local Ca2+ signaling in human arterial myocytes and suggests that these events may play an important role in control of cerebral artery diameter in humans.
Wellman
George C
GC
Department of Pharmacology, University of Vermont College of Medicine, Burlington, VT 05405-0068, USA. gwellman@zoo.uvm.edu.
Nathan
David J
DJ
Saundry
Christine M
CM
Perez
Guillermo
G
Bonev
Adrian D
AD
Penar
Paul L
PL
Tranmer
Bruce I
BI
Nelson
Mark T
MT
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002536:Cerebral Arteries / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004594:Electrophysiology; D005260:Female; D005456:Fluorescent Dyes; D006801:Humans; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism; D012433:Ryanodine / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects
D005456:Fluorescent Dyes; D051036:Large-Conductance Calcium-Activated Potassium Channels; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D012433:Ryanodine; D011188:Potassium