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Biomedical subjects

M Cahalan

Publications and source records attributed to M Cahalan.

7 recordsLinked to original sources

Cell-to-cell spread of calcium signals mediated by ATP receptors in mast cells.

Rat basophilic leukaemia cells, like mast cells from which they are derived, have surface Fc epsilon receptors that trigger secretion of inflammatory mediators when crosslinked. Both GTP-binding proteins and a rise in cytosolic calcium concentration ([Ca2+]i) are implicated in the secretory mechanism. Here we use a video-imaging technique to report that transient rises in [Ca2+]i initiated in an individual cell can spread from cell to cell in a wave-like pattern by means of a secreted intermediate, in the absence of gap-junctional communication. We find that the leukaemia cells, peritoneal mast cells and mucosal mast cells have cell-surface P2-type purinergic receptors that can trigger similar [Ca2+]i transients. We provide evidence that ATP is rapidly released, and that it can amplify [Ca2+]i signals and initial secretory responses during antigen-stimulation of rat basophilic leukaemia cells.

Animals

Comparison of the findings on preoperative dipyridamole perfusion scintigraphy and intraoperative transesophageal echocardiography: implications regarding the identification of myocardium at ischemic risk.

The evidence of myocardium at potential ischemic risk on preoperative dipyridamole perfusion scintigraphy was compared with that of manifest ischemia on intraoperative transesophageal echocardiography in 26 patients at high risk of a coronary event undergoing noncardiac surgery. The clinical outcome was also assessed. Induced intraoperative wall motion abnormalities were more common in patients and myocardial segments with, than in those without, a preoperative reversible perfusion defect (both p less than 0.05). Conversely, a preoperative reversible perfusion defect was more common in patients and segments with, than in those without, a new intraoperative wall motion abnormality (both p less than 0.05). Six patients, five with a reversible scintigraphic defect but only three with a new wall motion abnormality, had a hard perioperative ischemic event. Events occurred more often among patients with, than in those without, a reversible perioperative scintigraphic defect (5 [33%] of 15 vs. 1 [9%] of 11) but this difference did not reach significance (p = 0.14), probably owing to the sample size. Intraoperative wall motion abnormalities were all reversible and did not differentiate between risk groups; these findings were possibly influenced by treatment. These preliminary data support the known relation between reversible scintigraphic defects and perioperative events and identify another manifestation of ischemic risk in the relation between reversible scintigraphic defects and induced intraoperative wall motion abnormalities. The value of intraoperative echocardiography in identifying ischemia and guiding therapy in patients with a reversible scintigraphic abnormality should be further assessed.

Coronary Disease

TEA prevents inactivation while blocking open K+ channels in human T lymphocytes.

The whole-cell recording mode of the patch-clamp technique was used to study the effect of external tetraethylammonium ([TEA+]o) on the inactivating, voltage-dependent K+ channels of human T lymphocytes. TEA+ reduced the peak amplitude and slowed the time course of the K+ current decay during a depolarizing pulse, resulting in a crossover of the current records in the presence and absence of TEA+. In solutions with different [TEA+]o both the peak K+ current amplitude, lKpeak, and the time constant of the decay of the K+ current, tau d, were reduced in a dose-dependent manner, both with apparent binding constants, KD, of 12 mM. The integral of K+ current during a prolonged depolarizing pulse was unaltered in solutions with different [TEA+]o. The concentration dependence of [TEA+]o on lKpeak, tau d, and the unchanged current integral can be explained with a kinetic scheme in which open channels blocked by TEA+ cannot inactivate.

Cell Line

Sodium channel selectivity. Dependence on internal permeant ion concentration.

The selectivity of sodium channels in squid axon membranes was investigated with widely varying concentrations of internal ions. The selectivity ratio, PNa/PK, determined from reversal potentials decreases from 12.8 to 5.7 to 3.5 as the concentration of internal potassium is reduced from 530 to 180 to 50 mM, respectively. The internal KF perfusion medium can be diluted by tetramethylammonium (TMA), Tris, or sucrose solutions with the same decrease in PNa/PK. The changes in the selectivity ratio depend upon internal permeant ion concentration rather than ionic strength, membrane potential, or chloride permeability. Lowering the internal concentration of cesium, rubidium, guanidnium, or ammonium also reduces PNa/Pion. The selective sequence of the sodium channel is: Na greater than guanidinium greater than ammonium greater than K greater than Rb greater than Cs.

Animals