Passive leak

Despite this paucity of evidence for physiologically relevant VDCs or ROCs, influx of extracellular Ca is undoubtedly crucial for the maintenance of agonist-induced contraction of airway smooth muscle. In the absence of extracellular Ca, tissue strips of airway smooth muscle in vitro will fail to maintain a contraction in response to agonist stimulation, and the sustained plateau of elevated cytosolic Ca in Fura-2-loaded cells will be abolished (Fig. 9.2). One possible explanation for the net influx of extracellular Ca in these circumstances (in the absence of VDCs or ROCs) is that, in the continuing presence of agonist, mechanisms for removing intracellular Ca may be suppressed, thereby allowing the passive leak to provide sufficient Ca to raise cytosolic levels. 

The path of entry of extracellular Ca during the sustained phase of contraction in ASM has eluded definition in the absence, to date, of the demonstration of physiologically relevant VDCs or ROCs. These data raise the possibility that following agonist activation, when the buffering capacity of the sr is abolished, the passive plasmalemmal leak can provide sufficient extracellular Ca to sustain the onist-induced, or receptor-mediated (Murray and Kotlikoflf, 1991), plateau rise in cytosolic Ca which accompanies maintained contraction. 

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Can passive leak-limiting technology (e.g., blowout resistant gaskets and excess flow valves) be utilized to limit potential for loss of containment ... 

Cyclic GMP decreases basal and stimulated concentrations of intracellular Ca (Nakashima et al, 1986 Johansson and Haynes, 1992). A number of Ca handling systems have been identified in platelets including receptor operated channels, passive leak, Ca -ATPase extrusion pump, the NaV Ca exchanger, Ca -accumulating ATPase pump of the dense tubular membrane (an intraplatelet membrane Ca store) and passive leakage and receptor operated Ca chatinels in the dense tubular membrane. In principle, all these... 

The free Ca concentration in the extracellular fluid surrounding airway smooth muscle is approximately 1.5 mM, while cytosolic Ca " is below the micromolar range. The large electrochemical gradient across the plas-malemmal membrane results in a continuous passive leak of Ca into the cytosol. This leak of Ca into the cytosol is normally compensated for by the active Ca removal mechanisms (discussed later) which return Ca to the extracellular space, thereby preventing a rise in the cytosolic Ca concentration. 

In addition to this passive leak, extracellular Ca " may gain access to the cytosol by passing through ion channels in the cell membrane (Fig. 9.3). As for other smooth muscle, two types of Ca " channel have been proposed... 

The Ca " content of the sr is determined by a balance between the activity of the Ca -ATPase pump and mechanisms which release Ca " from the store (Fig. 9.3). These mechanisms include the opening of ion channels in the sr membrane in response to IP3 and passive leak of Ca out of the sr. Both of these processes involve the movement of Ca " " from the high concentration within the store, estimated to be 5 mM Ca (Leijten and van Breemen, 1984), to the low concentration (100 nM) within the cytosol. Functional studies in vascular smooth muscle have demonstrated that the quantity of Ca " " stored in the sr is sufficient to activate maximal... 

A.2 Plasnrnlemnud Ca -ATPase Pump Ca is extruded extracellularly from the cytosol by a Mg -dependent Ca, H -ATPase pump (Hogaboom and Fedan, 1981). This is an electrically neutral process by which Ca is exchanged ft)r 2H. In resting smooth muscle the Ca " pump exists in a low affinity state which is capable of extruding sufficient Ca " to maintain steady state in the fece of Ca influx across the plasmalemma down its concentration gradient via the passive leak mechanism (Carafoli, 1984). 

Because in most physiological circumstances oxygen consumption is controlled by energy metabolism, Ismail-Beigi and Edelman (22) proposed that the primary effect of thyroid hormones is to increase the amount of energy expended in translocating cations across cell membranes, probably as a response to an increased passive leak of sodium into, and potassium out of, cells. The extent to which this transport contributes to heat production and ATP utilization is uncertain. The stimulation of futile cycles by thyroid hormones (23) has been suggested to be an additional component of ATP disposal. 

Fig. 5. Schematic model for the ion movements aeross gastric microsomal vesicles. The J values are the ionic fluxes with the superseiipts designating pump flux (P) or leak pathway (L). The model consists of an ATP-driven exchange pump, (K +H )-ATPase, and the passive leak pathways for the...

Fission product containment Containment Passive Leak tight design... 

This is consistent with the fact that in Necturus the proximal tubule does not modify the filtered potassium load. There is no significant net transport, reabsorptive or secretory, in the Necturus proximal tubule. The observed electrical asymmetry of this epithelium may be due to the difference in magnitude of two K" " diffusion potentials in series. Thus the simultaneously observed activity distribution ratios can account for all the electrical asjmimetry without the need to invoke a significant effect of passive leak of Na" " on either membrane boundary. 

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