Calcium release waves

ATP is used not only to power muscle contraction, but also to re-establish the resting state of the cell. At the end of the contraction cycle, calcium must be transported back into the sarcoplasmic reticulum, a process which is ATP driven by an active pump mechanism. Additionally, an active sodium-potassium ATPase pump is required to reset the membrane potential by extruding sodium from the sarcoplasm after each wave of depolarization. When cytoplasmic Ca2- falls, tropomyosin takes up its original position on the actin and prevents myosin binding and the muscle relaxes. Once back in the sarcoplasmic reticulum, calcium binds with a protein called calsequestrin, where it remains until the muscle is again stimulated by a neural impulse leading to calcium release into the cytosol and the cycle repeats. 

Fig. 10. The effect of different concentrations of the ionophore X 537 A on calcium release, by sarcoplasmic reticulum vesicles11S. The reaction mixture contained 20 mM Tris-maleate pH 6-8, 50 mM KC1, 10 mM MgClj, 0.1 mM CaCl2, 0.1 mM murexide and 0.27 mg protein/ml. Calcium uptake and release were followed by monitoring the changes in the absorbance undergone by murexide. The measurements were performed with a filter dual wave length (540—507 nm) double beam spectrophotometer...

Cardiac muscle ceiis are dependent on both extra- and intracellular stores of calcium. The wave of depolarization traveling along the cell fiber appears to induce the flow of extracellular Ca into the cell. The rise in cytosolic calcium that results is not sufficient to cause contraction of the cardiac muscle. Instead, it seems to induce a more substantial release of calcium from the SR of the cardiac muscle cell, which then stimulates contraction. 

This is considerably smaller than the individual subunit size of the three main RyRs found in mammalian cells. Its localization to the egg cortex contradicts evidence from confocal fluorescent microscopy, which indicates that ryanodine receptors can mediate the propagation of calcium waves deep into the egg cytoplasm (Galione et al, 1993a). Whether this protein is modulated by cADPR is unknown. However, cADPR has also been shown to activate calcium release in mammalian cells, where the RyRs are better characterized (see Section IV.B.2). 

Galione, A., A. McDougall, W.B. Busa, N. Willmott, I. Gillot M. Whitaker. 1993. Redundant mechanisms of calcium-induced calcium release underlying calcium waves during fertilization of sea urchin eggs. Science 261 348-52. 

From a distance, the cycles of calcium release and return look like waves of calcium washing through the cell. Heart muscle beats steadily by timing the calcium waves from its sarcoplasmic reticulum in a rhythmic calcium clock pattern. Other cells pick up on the beat set by one calcium clock, coordinating in a pacemaker symphony. Because the calcium ions are charged, this chemical wave is electrical, too, and can be coordinated with an electrical pacemaker. 

In muscle there is an extensive endoplasmic reticulum called the sarcoplasmic reticulum. It seems to be primarily concerned with regulating Ca " ion fluxes during the contraction-relaxation cycle. The components of the sarcoplasmic reticulum are in contact with invaginations of the cell membrane which conduct the wave of depolarization into the interior of the muscle cell and to the myofibrils. Relaxation of muscle is brought about by accumulation of calcium within the sarcoplasmic reticulum, whereas contraction occurs as a consequence of an increase in calcium released from the sarcoplasmic reticulum secondary to an... 

The sequence of events that result in neurotransmission of information from one nerve cell to another across the s)mapses begins with a wave of depolarization which passes down the axon and results in the opening of the voltage-sensitive calcium charmels in the axonal terminal. These charmels are frequently concentrated in areas which correspond to the active sites of neurotransmitter release. A large (up to 100 M) but brief rise in the calcium concentration within the nerve terminal triggers the movement of the synaptic vesicles, which contain the neurotransmitter, towards the synaptic membrane. By means of specific membrane-bound proteins (such as synaptobrevin from the neuronal membrane and synaptotagrin from the vesicular membrane) the vesicles fuse with the neuronal membrane and release their contents into the synaptic gap by a process of exocytosis. Once released of their contents, the vesicle membrane is reformed and recycled within the neuronal terminal. This process is completed once the vesicles have accumulated more neurotransmitter by means of an energy-dependent transporter on the vesicle membrane (Table 2.3). 

In patients with unstable angina, immediate-release short-acting calcium channel blockers can increase the risk of adverse cardiac events and therefore are contraindicated (see Toxicity, above). However, in patients with non-Q-wave myocardial infarction, diltiazem can decrease the frequency of postinfarction angina and may be used. 

T tubules (Chapter 19, Section B,4 Fig. 19-21), a wave of depolarization initiates the release of calcium and muscular contraction. 

T-type calcium channels play critical roles in shaping the electrical and plastic properties of neurons and are also implicated in hormone secretion, differentiation and muscle development (Huguenard, 1996 Perez-Reyes, 2003). In thalamic reticular and relay neurons, T-type channels contribute to rhythmic rebound burst firing and spindle waves associated with slow-wave sleep. T-type channels also play crucial roles in dendritic integration and calcium-mediated spiking in hippocampal pyramidal cells, and in synaptic release at olfactory dendrodendritic... 

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