Ca2+ sparks and their function in human cerebral arteries

Abstract

Background and Purpose - 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 μm2 (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.