Background and Purpose
—
Local Ca
2+
release events (Ca
2+
sparks) caused by the opening of ryanodine-sensitive Ca
2+
channels in the sarcoplasmic reticulum have been suggested to oppose constriction in cerebral arteries through the activation of large-conductance Ca
2+
-activated K
+
(BK) channels. We report the first identification and characterization of Ca
2+
sparks and associated BK channel currents in smooth muscle cells isolated from human cerebral arteries.
Methods
—
Membrane currents and intracellular Ca
2+
were measured with the use of the patch-clamp technique and laser scanning confocal microscopy.
Results
—
Ca
2+
sparks with a peak fractional fluorescence change (F/F
0
) of 2.02±0.04 and size of 8.2±0.5 μm
2
(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, Ca
2+
sparks (61 of 85 sparks) were associated with transient BK currents. Consistent with a role for Ca
2+
sparks in the control of cerebral artery diameter, agents that block Ca
2+
sparks (ryanodine) or BK channels (iberiotoxin) were found to contract human cerebral arteries.
Conclusions
—
This study provides evidence for local Ca
2+
signaling in human arterial myocytes and suggests that these events may play an important role in control of cerebral artery diameter in humans.
