Ryanodine receptors regulate arterial diameter and wall [Ca2+] in cerebral arteries of rat via Ca2+‐dependent K+ channels
1 The effects of inhibitors of ryanodine‐sensitive calcium release (RyR) channels in the
sarcoplasmic reticulum (SR) and Ca2+‐dependent potassium (KCa) channels on the
membrane potential, intracellular [Ca2+], and diameters of small pressurized (60 mmHg)
cerebral arteries (100‐200 μm) were studied using digital fluorescence video imaging of
arterial diameter and wall [Ca2+], combined with microelectrode measurements of arterial
membrane potential. 2 Ryanodine (10 μM), an inhibitor of RyR channels, depolarized by 9 …
sarcoplasmic reticulum (SR) and Ca2+‐dependent potassium (KCa) channels on the
membrane potential, intracellular [Ca2+], and diameters of small pressurized (60 mmHg)
cerebral arteries (100‐200 μm) were studied using digital fluorescence video imaging of
arterial diameter and wall [Ca2+], combined with microelectrode measurements of arterial
membrane potential. 2 Ryanodine (10 μM), an inhibitor of RyR channels, depolarized by 9 …
- 1The effects of inhibitors of ryanodine‐sensitive calcium release (RyR) channels in the sarcoplasmic reticulum (SR) and Ca2+‐dependent potassium (KCa) channels on the membrane potential, intracellular [Ca2+], and diameters of small pressurized (60 mmHg) cerebral arteries (100‐200 μm) were studied using digital fluorescence video imaging of arterial diameter and wall [Ca2+], combined with microelectrode measurements of arterial membrane potential.
- 2Ryanodine (10 μM), an inhibitor of RyR channels, depolarized by 9 mV, increased intracellular [Ca2+] by 46 nM and constricted pressurized (to 60 mmHg) arteries with myogenic tone by 44 μm (≈22 %). Iberiotoxin (100 nM), a blocker of KCa channels, under the same conditions, depolarized the arteries by 10 mV, increased arterial wall calcium by 51 nM, and constricted by 37 μm (≈19 %). The effects of ryanodine and iberiotoxin were not additive and were blocked by inhibitors of voltage‐dependent Ca2+ channels.
- 3Caffeine (10 mM), an activator of RyR channels, transiently increased arterial wall [Ca2+] by 136 ± 9 nM in control arteries and by 158 ± 12 nM in the presence of iberiotoxin. Caffeine was relatively ineffective in the presence of ryanodine, increasing [calcium] by 18 ± 5 nM.
- 4In the presence of blockers of voltage‐dependent Ca2+ channels (nimodipine, diltiazem), ryanodine and inhibitors of the SR calcium ATPase (thapsigargin, cyclopiazonic acid) were without effect on arterial wall [Ca2+] and diameter.
- 5These results suggest that local Ca2+ release originating from RyR channels (Ca2+ sparks) in the SR of arterial smooth muscle regulates myogenic tone in cerebral arteries solely through activation of KCa channels, which regulate membrane potential through tonic hyperpolarization, thus limiting Ca2+ entry through L‐type voltage‐dependent Ca2+ channels. KCa channels therefore act as a negative feedback control element regulating arterial diameter through a reduction in global intracellular free [Ca2+].
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