Block of neuronal apoptosis by a sustained increase of steady-state free Ca2+ concentration

Author(s):  
James L. Franklin ◽  
Eugene M. Johnson
1991 ◽  
Vol 261 (2) ◽  
pp. C253-C258 ◽  
Author(s):  
E. Suematsu ◽  
M. Resnick ◽  
K. G. Morgan

The mechanism of contraction of vascular smooth muscle by prostaglandin F2 alpha (PGF2 alpha) was examined by simultaneous measurement of the intracellular Ca2+ concentration [( Ca2+]i), force, and myosin light-chain (MLC) phosphorylation in ferret aorta. In the presence of 2.5 mM extracellular Ca2+, PGF2 alpha (10(-5)M) produced a tonic contraction with a transient spike in [Ca2+]i, followed by a relatively small sustained increase in [Ca2+]i (from a basal level of 2.32 +/- 0.07 x 10(-7) to 2.72 +/- 0.05 x 10(-7) M). In Ca(2+)-free bathing media, PGF2 alpha also produced a tonic contraction with a small spike in [Ca2+]i, indicating a release of Ca2+ from intracellular store sites, followed by no significant increase in [Ca2+]i. Ca(2+)-force curves were constructed by plotting the calibrated steady-state aequorin light signal against the resulting steady-state force. The curve was significantly shifted to the left by PGF2 alpha. PGF2 alpha also shifted the Ca(2+)-phosphorylation curve to the left. These results suggest that PGF2 alpha causes contraction by both elevating [Ca2+]i and decreasing the Ca2+ requirement for MLC phosphorylation. The data are consistent with a mechanism where there is either an increase in activity of MLC kinase or a decrease in phosphatase activity. Additionally, there was a smaller, but statistically significant, effect to increase force at any one phosphorylation level, pointing to the possibility of regulation of contractile force separate from MLC phosphorylation.


2008 ◽  
Vol 99 (6) ◽  
pp. 2844-2863 ◽  
Author(s):  
Nadja Spitzer ◽  
Gennady Cymbalyuk ◽  
Hongmei Zhang ◽  
Donald H. Edwards ◽  
Deborah J. Baro

A fundamental question in systems biology addresses the issue of how flexibility is built into modulatory networks such that they can produce context-dependent responses. Here we examine flexibility in the serotonin (5-HT) response system that modulates the cycle frequency (cf) of a rhythmic motor output. We found that depending on the preparation, the same 5-min bath application of 5-HT to the pyloric network of the California spiny lobster, Panulirus interruptus, could produce a significant increase, decrease, or no change in steady-state cf relative to baseline. Interestingly, the mean circuit output was not significantly different among preparations prior to 5-HT application. We developed pharmacological tools to examine the preparation-to-preparation variability in the components of the 5-HT response system. We found that the 5-HT response system consisted of at least three separable components: a 5-HT2βPan-like component mediated a rapid decrease followed by a sustained increase in cf; a 5-HT1αPan-like component produced a small and usually gradual increase in cf; at least one other component associated with an unknown receptor mediated a sustained decrease in cf. The magnitude of the change in cf produced by each component was highly variable, so that when summed they could produce either a net increase, decrease, or no change in cf depending on the preparation. Overall, our research demonstrates that the balance of opposing components of the 5-HT response system determines the direction and magnitude of 5-HT–induced change in steady-state cf relative to baseline.


2006 ◽  
Vol 290 (1) ◽  
pp. C152-C164 ◽  
Author(s):  
Kirk L. Hamilton ◽  
Matt Kiessling

We investigated the effects of 5,6-dichloro-1-ethyl-1,3-dihydro-2 H-benzimidazol-2-one(DCEBIO) on the Cl−secretory response of the mouse jejunum using the Ussing short-circuit current ( Isc) technique. DCEBIO stimulated a concentration-dependent, sustained increase in Isc(EC5041 ± 1 μM). Pretreating tissues with 0.25 μM forskolin reduced the concentration-dependent increase in Iscby DCEBIO and increased the EC50(53 ± 5 μM). Bumetanide blocked (82 ± 5%) the DCEBIO-stimulated Iscconsistent with Cl−secretion. DCEBIO was a more potent stimulator of Cl−secretion than its parent molecule, 1-ethyl-2-benzimidazolinone. Glibenclamide or NPPB reduced the DCEBIO-stimulated Iscby >80% indicating the participation of CFTR in the DCEBIO-stimulated Iscresponse. Clotrimazole reduced DCEBIO-stimulated Iscby 67 ± 15%, suggesting the participation of the intermediate conductance Ca2+-activated K+channel (IKCa) in the DCEBIO-activated Iscresponse. In the presence of maximum forskolin (10 μM), the DCEBIO response was reduced and biphasic, reaching a peak response of the change in Iscof 43 ± 5 μA/cm2and then falling to a steady-state response of 17 ± 10 μA/cm2compared with DCEBIO control tissues (61 ± 6 μA/cm2). The forskolin-stimulated Iscin the presence of DCEBIO was reduced compared with forskolin control tissues. Similar results were observed with DCEBIO and 8-BrcAMP where adenylate cyclase was bypassed. H89, a PKA inhibitor, reduced the DCEBIO-activated Isc, providing evidence that DCEBIO increased Cl−secretion via a cAMP/PKA-dependent manner. These data suggest that DCEBIO stimulates Cl−secretion of the mouse jejunum and that DCEBIO targets components of the Cl−secretory mechanism.


Author(s):  
R. C. Moretz ◽  
G. G. Hausner ◽  
D. F. Parsons

Use of the electron microscope to examine wet objects is possible due to the small mass thickness of the equilibrium pressure of water vapor at room temperature. Previous attempts to examine hydrated biological objects and water itself used a chamber consisting of two small apertures sealed by two thin films. Extensive work in our laboratory showed that such films have an 80% failure rate when wet. Using the principle of differential pumping of the microscope column, we can use open apertures in place of thin film windows.Fig. 1 shows the modified Siemens la specimen chamber with the connections to the water supply and the auxiliary pumping station. A mechanical pump is connected to the vapor supply via a 100μ aperture to maintain steady-state conditions.


2021 ◽  
Author(s):  
Wu Lan ◽  
Yuan Peng Du ◽  
Songlan Sun ◽  
Jean Behaghel de Bueren ◽  
Florent Héroguel ◽  
...  

We performed a steady state high-yielding depolymerization of soluble acetal-stabilized lignin in flow, which offered a window into challenges and opportunities that will be faced when continuously processing this feedstock.


2008 ◽  
Vol 45 ◽  
pp. 161-176 ◽  
Author(s):  
Eduardo D. Sontag

This paper discusses a theoretical method for the “reverse engineering” of networks based solely on steady-state (and quasi-steady-state) data.


1979 ◽  
Vol 1 (4) ◽  
pp. 13-24
Author(s):  
E. Dahi ◽  
E. Lund
Keyword(s):  

2002 ◽  
Vol 16 (2) ◽  
pp. 71-81 ◽  
Author(s):  
Caroline M. Owen ◽  
John Patterson ◽  
Richard B. Silberstein

Summary Research was undertaken to determine whether olfactory stimulation can alter steady-state visual evoked potential (SSVEP) topography. Odor-air and air-only stimuli were used to determine whether the SSVEP would be altered when odor was present. Comparisons were also made of the topographic activation associated with air and odor stimulation, with the view toward determining whether the revealed topographic activity would differentiate levels of olfactory sensitivity by clearly identifying supra- and subthreshold odor responses. Using a continuous respiration olfactometer (CRO) to precisely deliver an odor or air stimulus synchronously with the natural respiration, air or odor (n-butanol) was randomly delivered into the inspiratory airstream during the simultaneous recording of SSVEPs and subjective behavioral responses. Subjects were placed in groups based on subjective odor detection response: “yes” and “no” detection groups. In comparison to air, SSVEP topography revealed cortical changes in response to odor stimulation for both response groups, with topographic changes evident for those unable to perceive the odor, showing the presence of a subconscious physiological odor detection response. Differences in regional SSVEP topography were shown for those who reported smelling the odor compared with those who remained unaware of the odor. These changes revealed olfactory modulation of SSVEP topography related to odor awareness and sensitivity and therefore odor concentration relative to thresholds.


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