This article shows that colchicine and taxol strongly influence the kinetics of L-type Ca channels in intact cardiac cells, and it suggests a mechanism for this action. It is known that colchicine disassociates microtubules into tubulin, and that taxol stabilizes microtubules. We have found that colchicine increases the probability that Ca channels are in the closed state and that taxol increases the probability they are in the open state. Moreover, taxol lengthens the mean open time of Ca channels. In this regard, taxol is similar to Bay-K 8644; however, Bay K works on inside-out patches, but taxol does not. Neither colchicine nor taxol alters the number of Ca channels in a patch. We have quantified these results as follows. It is known that L-type channels in embryonic chick heart ventricle cells have voltage- and current-dependent inactivation. In 10 mM Ba, channel conductance is linear in the range -10 to 20 mV. The conductance is 12 +/- 1 pS, and the extrapolated reversal potential is 42 +/- 2 mV (n = 3). In cell-attached patches, inactivation depends on the number of channels. One channel (holding at -80 mV and stepping to 0 mV for 500 ms) shows virtually no inactivation. However, three channels inactivate with a time constant of 360 +/- 20 ms (n = 6). In similar patches, colchicine (80 microM for 15 min) decreases the inactivation time constant to 162 +/- 33 ms (n = 4) and taxol (50 microM for 10 min) virtually abolishes inactivation (time constant 812 +/- 265 ms (n = 4)). We suggest that colchicine and taxol affect Ca channels through their action on the cytoskeleton, which in turn regulates the effective concentration of inactivating ions near the mouths of channels. An alternate explanation is that free tubulin interacts directly with Ca channels.
Aims. We analyze optical and X-ray observations of GRB 050904 obtained with TAROT and SWIFT. Methods. We perform temporal and spectral analysis of the X-ray and optical data. Results. We find significant absorption in the early phase of the X-ray light curve, with some evidence (3σ level) of variability. We interpret this as a progressive photo-ionization. We investigate the environment of the burst and constrain its density profile. We find that the overall behavior of the afterglow is compatible with a fireball expanding in a wind environment during the first 2000 s after the burst (observer frame). On the other hand, the late (after 0.5 days, observer frame) afterglow is consistent with an interstellar medium, suggesting the possible presence of a termination shock. We estimate the termination shock position to be R t ∼ 1.8 × 10 −2 pc, and the wind density parameter to be A * ∼ 1.8. We try to explain the simultaneous flares observed in optical and X-ray bands in light of different models: delayed external shock from a thick shell, inverse Compton emission from reverse shock, inverse Compton emission from late internal shocks or a very long internal shock activity. Among these models, those based on a single emission mechanism, are unable to account for the broad-band observations. Models invoking late internal shocks, with the inclusion of IC emission, or a properly tuned very long internal shock activity, offer possible explanations.
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