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Role of ryanodine receptors in acidic pH‐induced dilation of brain parenchymal arterioles
Author(s) -
Dabertrand Fabrice,
Nelson Mark T.,
Brayden Joseph E.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1024.15
Subject(s) - ryanodine receptor , chemistry , vascular smooth muscle , biophysics , extracellular , vasodilation , bk channel , contraction (grammar) , endoplasmic reticulum , medicine , membrane potential , smooth muscle , biochemistry , biology
Ryanodine receptors (RyRs) are Ca 2+ permeable channels in the sarcoplasmic reticulum. RyRs regulate vascular smooth muscle cell (VSMC) membrane potential through their localized Ca 2+ ‐release events, termed Ca 2+ sparks, which activate hyperpolarizing BK currents leading to vasodilation. This mechanism is clearly demonstrated by the non‐additive constrictions induced by RyR or BK channel blockers in pressurized pial arteries. However these blockers have little effect on the diameter of pressurized parenchymal arterioles (PAs) from the brain, even though functional BK channels and RyRs are present. At normal pH (7.4), VSMCs in pressurized PAs exhibit largely Ca 2+ waves but not Ca 2+ sparks. Alkaline pH has been shown to shift Ca 2+ sparks to Ca 2+ waves in pial arteries. Therefore, we hypothesized that acidic pH might dilate PAs by reshaping the intracellular Ca 2+ dynamic from Ca 2+ waves to Ca 2+ sparks, thereby activating BK channels. As predicted, reducing extracellular pH from 7.4 to 7.0 dramatically decreased Ca 2+ wave activity, and increased spark activity. Acidic pH caused a dilation of up to 70% of the maximal diameter, and this dilation was inhibited by about 60% by BK or RyR blockers. These findings suggest that RyRs play a major role in the acidic pH‐induced dilation of PAs through Ca 2+ spark‐mediated activation of BK channels. Supported by AHA 09POST2290090 (FD) and the NIH HL095488, HL44455 and HL58231.