PubMed · 9115729
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B W Connors, Y Amitai. 1997. Making waves in the neocortex.. https://doi.org/10.1016/s0896-6273(00)81236-2
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1. Single cell fluorimetry was used to monitor caffeine-induced oscillations of cytosolic [Ca2+] in frog sympathetic ganglion neurones in 2.0 mM K+ Ringer solution. 2. [Ca2+] oscillations decreased in frequency and exhibited three different amplitude patterns after the first large peak of [Ca2+]: (a) a series of big oscillations (BOs) of constant large amplitude (300-400 nM), (b) a series of much smaller oscillations (SOs) (40-60 nM), or (c) a series of decaying oscillations (DOs) of rapidly decreasing amplitude. 3. A model in which the oscillation amplitude was determined by the Ca2+ content of the endoplasmic reticulum (ER) whereas the oscillation frequency was controlled by how rapidly the cytosolic [Ca2+] reached the threshold for Ca2+-induced Ca2+ release (CICR) was able to simulate each observed pattern by varying the level of activity of the ER Ca2+ pump (SERCA), CICR and release-activated Ca2+ transport (RACT). A cumulative, cytosolic Ca2+-dependent inactivation of the plasma membrane (PM) Ca2+ influx or of the Ca2+-sensitive leak coefficient of the ryanodine receptors caused the oscillation frequency to decrease in the model. 4. Transitions between BOs and SOs and changes in [Ca2+] oscillations caused by ryanodine, thapsigargin, lanthanum and FCCP could also be simulated. 5. We conclude that RACT, SERCA, CICR and Ca2+-dependent PM Ca2+ influx are major mechanisms underlying [Ca2+] oscillations in these neurones.
1. Intracellular Ca2+ ([Ca2+]i) signals were studied with spatial resolution in bovine vascular endothelial cells using the fluorescent Ca2+ indicator fluo-3 and confocal laser scanning microscopy. Single cells were stimulated with the purinergic receptor agonist ATP resulting in an increase of [Ca2+]i due to intracellular Ca2+ release from inositol 1,4,5-trisphosphate (IP3)-sensitive stores. ATP-induced Ca2+ release was quantal, i.e. submaximal concentrations mobilized only a fraction of the intracellularly stored Ca2+. 2. Focal receptor stimulation in Ca2+-free solution by pressure application of agonist-containing solution through a fine glass micropipette resulted in a spatially restricted increase in [Ca2+]i. Ca2+ release was initiated at the site of stimulation and frequently propagated some tens of micrometres into non-stimulated regions. 3. Local Ca2+ release caused activation of capacitative Ca2+ entry (CCE). CCE was initially colocalized with Ca2+ release. Following repetitive focal stimulation, however, CCE became detectable at remote sites where no Ca2+ release had been observed. In addition, the rate of Ca2+ store depletion with repetitive local activation of release in Ca2+-free solution was markedly slower than that elicited by ATP stimulation of the entire cell. 4. From these experiments it is concluded that both intracellular IP3-dependent Ca2+ release and activation of CCE are controlled locally at the subcellular level. Moreover, redistribution of intracellular Ca2+ stored within the endoplasmic reticulum efficiently counteracts local store depletion and accounts for the spatial spread of CCE activation.
Antidepressants and neuroleptic drugs are sometimes the reason for the occurrence of the polymorphic ventricular arrhythmia torsades de pointes in patients. Therefore, it was of interest to study the actions of some of these drugs such as imipramine, amitriptyline, doxepin, chlorpromazine, trifluoperazine and thioridazine in isolated, spontaneously beating Purkinje fibers of guinea-pig hearts using the intracellular microelectrode technique because experimentally induced early afterdepolarizations (EADs) may be associated with this special type of arrhythmia. If the extracellular K+ concentration was 2.7mM none of these drugs could elicit EADs. For that reason the K+ concentration was lowered to 1. 35mM and EADs were evoked by imipramine (2 and 5 microM). Amitriptyline (2 and 5 microM) and doxepin (2 microM) did not induce EADs. Only a concentration of 5 microM doxepin elicited EADs. Among the neuroleptic drugs, chlorpromazine at a concentration of 2 and 5 microM was responsible for the occurrence of EADs as well as thioridazine in the same concentrations. When trifluoperazine (2 and 5 microM) was applied no EADs could be observed. Tetrodotoxin (0. 2 microMl-1) abolished thioridazine-induced EADs. Several membrane depolarizing currents may participate in the initiation of these EADs. Our results demonstrate that in guinea-pig Purkinje fibers some tricyclic antidepressants and some neuroleptic drugs are responsible for the rare occurrence of EADs under hypokalemic conditions.