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Caffeine and K + ‐induced depolarization increase and ryanodine decreases frequency of Ca 2+ sparks in the spiral modiolar artery
Author(s) -
Regehr Keil,
Liang Chengya,
Wangemann Philine
Publication year - 2006
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.20.4.a287
Subject(s) - ryanodine receptor , depolarization , caffeine , chemistry , biophysics , contraction (grammar) , medicine , endoplasmic reticulum , biology , biochemistry
Ryanodine receptors (RyR) have been shown to mediate dilation in arterial smooth muscle via Ca 2+ sparks. The goal of this study was to determine whether 1 μM ryanodine (Ry), 1 mM caffeine (Caf) and 38 mM K + increases spark frequency and/or amplitude in the gerbil spiral modiolar artery (SMA). SMA diameter was monitored by video microscopy, and Ca 2+ sparks were visualized with fluo‐4. Ry caused a dilation; K + and Caf caused a transient constriction. Sparks had a frequency of 2.7 ± 0.3 Hz, a rise time (0–100%) of 16.6 ± 0.8 ms and a half‐decay time of 22 ± 2 ms (n=25). Ry reduced spark frequency from 2.4 ± 0.4 to 0.6 ± 0.2 Hz (n=11). K + and Caf increased spark frequency from 2.3 ± 0.3 to 3.5 ± 0.3 Hz (n=21) and 4.7 ± 1.0 Hz (n=6). These findings suggest that 1) the Ry induced high open probability subconductance state of the RyR causes Ca 2+ to leak from the SR and accumulate to sufficiently high concentrations to activate BK K + channels; 2) Caf stimulates RyR to leak Ca 2+ to accumulate to concentrations that activates the contractile apparatus; and 3) K + depolarization opens L‐type Ca 2+ channels, elevating Ca 2+ influx and loading of the SR leading to an activation of the RyR. NIH‐R01‐DC04280