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Functional Coupling of Ryanodine Receptors to K(Ca )Channels in Smooth Muscle Cells from Rat Cerebral Arteries
The relationship between Ca(2+) release (“Ca(2+) sparks”) through ryanodine-sensitive Ca(2+) release channels in the sarcoplasmic reticulum and K(Ca) channels was examined in smooth muscle cells from rat cerebral arteries. Whole cell potassium currents at physiological membrane potentials (−40 mV) a...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
1999
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2223357/ https://www.ncbi.nlm.nih.gov/pubmed/9925821 |
Sumario: | The relationship between Ca(2+) release (“Ca(2+) sparks”) through ryanodine-sensitive Ca(2+) release channels in the sarcoplasmic reticulum and K(Ca) channels was examined in smooth muscle cells from rat cerebral arteries. Whole cell potassium currents at physiological membrane potentials (−40 mV) and intracellular Ca(2+) were measured simultaneously, using the perforated patch clamp technique and a laser two-dimensional (x–y) scanning confocal microscope and the fluorescent Ca(2+) indicator, fluo-3. Virtually all (96%) detectable Ca(2+) sparks were associated with the activation of a spontaneous transient outward current (STOC) through K(Ca) channels. A small number of sparks (5 of 128) were associated with currents smaller than 6 pA (mean amplitude, 4.7 pA, at −40 mV). Approximately 41% of STOCs occurred without a detectable Ca(2+) spark. The amplitudes of the Ca(2+) sparks correlated with the amplitudes of the STOCs (regression coefficient 0.8; P < 0.05). The half time of decay of Ca(2+) sparks (56 ms) was longer than the associated STOCs (9 ms). The mean amplitude of the STOCs, which were associated with Ca(2+) sparks, was 33 pA at −40 mV. The mean amplitude of the “sparkless” STOCs was smaller, 16 pA. The very significant increase in K(Ca )channel open probability (>10(4)-fold) during a Ca(2+) spark is consistent with local Ca(2+) during a spark being in the order of 1–100 μM. Therefore, the increase in fractional fluorescence (F/F(o)) measured during a Ca(2+) spark (mean 2.04 F/F(o) or ∼310 nM Ca(2+)) appears to significantly underestimate the local Ca(2+) that activates K(Ca )channels. These results indicate that the majority of ryanodine receptors that cause Ca(2+) sparks are functionally coupled to K(Ca) channels in the surface membrane, providing direct support for the idea that Ca(2+) sparks cause STOCs. |
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