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Rapid Activation of the Cardiac Ryanodine Receptor by Submillisecond Calcium Stimuli
- Source :
- The Journal of General Physiology
- Publication Year :
- 1999
- Publisher :
- Rockefeller University Press, 1999.
-
Abstract
- The local control concept of excitation–contraction coupling in the heart postulates that the activity of the sarcoplasmic reticulum ryanodine receptor channels (RyR) is controlled by Ca2+entry through adjoining sarcolemmal single dihydropyridine receptor channels (DHPRs). One unverified premise of this hypothesis is that the RyR must be fast enough to track the brief (2+elevations accompanying single DHPR channel openings. To define the kinetic limits of effective trigger Ca2+signals, we recorded activity of single cardiac RyRs in lipid bilayers during rapid and transient increases in Ca2+generated by flash photolysis of DM-nitrophen. Application of such Ca2+spikes (amplitude ∼10–30 μM, duration ∼0.1–0.4 ms) resulted in activation of the RyRs with a probability that increased steeply (apparent Hill slope ∼2.5) with spike amplitude. The time constants of RyR activation were 0.07–0.27 ms, decreasing with spike amplitude. To fit the rising portion of the open probability, a single exponential function had to be raised to a powern∼ 3. We show that these data could be adequately described with a gating scheme incorporating four sequential Ca2+-sensitive closed states between the resting and the first open states. These results provide evidence that brief Ca2+triggers are adequate to activate the RyR, and support the possibility that RyR channels are governed by single DHPR openings. They also provide evidence for the assumption that RyR activation requires binding of multiple Ca2+ions in accordance with the tetrameric organization of the channel protein.
- Subjects :
- Patch-Clamp Techniques
cardiac muscle
Physiology
Lipid Bilayers
Gating
Acetates
In Vitro Techniques
calcium signaling
010402 general chemistry
Models, Biological
01 natural sciences
03 medical and health sciences
Dogs
Microsomes
ryanodine receptor
Animals
Patch clamp
Lipid bilayer
Chelating Agents
030304 developmental biology
Calcium signaling
0303 health sciences
Photolysis
gating model
Chemistry
Ryanodine receptor
Myocardium
Endoplasmic reticulum
Time constant
Heart
Ryanodine Receptor Calcium Release Channel
musculoskeletal system
Ethylenediamines
sarcoplasmic reticulum
0104 chemical sciences
Coupling (electronics)
Kinetics
Biochemistry
Biophysics
Calcium
Original Article
tissues
Ion Channel Gating
Algorithms
Subjects
Details
- ISSN :
- 15407748 and 00221295
- Volume :
- 114
- Database :
- OpenAIRE
- Journal :
- The Journal of General Physiology
- Accession number :
- edsair.doi.dedup.....d9c597aa01ee3471fc851e49cfaa6f95