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Query: UMLS:C0848283 (rundown)
 502 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The effects of inhibiting phosphatase activity on Ca(2+)-channel currents and cell shortening in single cells of the guinea-pig taenia caeci were investigated by whole-cell voltage clamp and video recording techniques. 2. Ca(2+)-channel currents were isolated by use of pipette solutions containing Cs, tetraethylammonium and adenosine triphosphate (ATP) (3 mM). Ca2+ or Ba2+ (7.5 mM) in the bathing solution acted as the charge carrier during inward current flow. 3. Ca(2+)-channel currents in 7.5 mM Ba2+ (IBa) were recorded at potentials positive to -40 mV, were maximal near 0 mV and reversed near +60 mV. Both the inward and outward flow of current was blocked by 100 microM Cd2+. 4. Addition of the ATP analogue, adenosine 5'-O(3-thiotriphosphate) (ATP gamma S) (1 mM) to the pipette solution (containing 3 mM ATP) caused cell shortening to 23 +/- 2% (n = 5) of their initial length within 5 min. Control cells (containing 4 mM ATP) did not contract during recording periods up to 60 min in duration. 5. IBa, recorded 1-2 min after membrane rupture, was 134 +/- 19 (n = 13) pA, compared with 209 +/- 25 (n = 5) pA in control cells, otherwise there were no significant time-dependent effects of ATP gamma S. In particular, ATP gamma S did not prevent the decrease in amplitude, nor the acceleration of inactivation when Ca2+ (7.5 mM) replaced Ba2+ as the permeating ion. 6. Okadaic acid (OA) (50 microM), a chemical inhibitor of phosphatase activity, produced similar effects when applied intracellularly. When OA (25,microM) was applied extracellularly the rate of rundown of 'Ba was slowed. 7. Isoprenaline (1 microM) alone had no effect on 'Ba, but induced a small increase in IBa in the presence of OA (25 microM). 8. Thus, our results indicate that (1) the contractions in ATP gamma S and OA may well arise from the activation of a kinase which phosphorylates myosin at low concentrations of Ca2 +, and (2) changes in the state of phosphorylation of Ca2+ channels, or associated proteins, in the taenia caeci modulate their function, but probably not via mechanisms involving cyclic AMP-dependent protein kinases.
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PMID:Effects of okadaic acid and ATP gamma S on cell length and Ca(2+)-channel currents recorded in single smooth muscle cells of the guinea-pig taenia caeci. 166 31

Metabolic pathways in vascular smooth muscles (VSM) appear to be functionally compartmentalized such that glycolysis fuels membrane-related processes, whereas oxidative processes fuel actin-myosin interaction. Because ATP influences Ca2+ channel activity, we examined the effects of ATP and metabolic substrates on Ca2+ channel activity with patch-clamp techniques in VSM cells isolated from rat portal vein. The peak magnitude of the Ca2+ channel currents was found to depend on the ATP concentration in the patch pipette. Cells perfused with 1, 3, and 5 mMATP had mean peak currents of 4.7 +/- 0.6, 12.2 +/- 1.9, and 17.6 +/- 2.0 pA/pF, respectively, and all currents showed substantial rundown. In separate experiments performed in the absence of intracellular ATP, provision of glycolytic but not oxidative substrates was able to maintain Ca2+ channel currents at levels comparable with those seen in the presence of 1 mM ATP. In the presence of 5 mM ATP, provision of glycolytic substrates resulted in a high peak current amplitude that was also very stable. Finally, metabolic inhibition with cyanide and iodoacetate caused a significant increase in the rate of current rundown, even in the presence of 5 mM ATP. These findings indicate that Ca2+ channel current is strongly dependent on ATP and that the source of ATP can also be an important factor. Compared with exogenous provision of ATP, endogenous metabolism preferentially maintained Ca2+ channel currents, consistent with the hypothesis of a functionally separate subsarcolemmal compartment. This provides an effective pathway for linking E-C coupling and vascular contractility to the metabolic state of the vascular cell.
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PMID:Dependence of Ca2+ channel currents on endogenous and exogenous sources of ATP in portal vein smooth muscle. 912 63

The functional diversity of the actin microfilaments relies in part on the actin binding protein tropomyosin (Tm). The muscle-specific Tms regulate actin-myosin interactions and hence contraction. However, there is less known about the roles of the numerous cytoskeletal isoforms. We have shown previously that a cytoskeletal Tm, Tm5NM1, defines a Z-line adjacent cytoskeleton in skeletal muscle. Recently, we identified a second cytoskeletal Tm in this region, Tm4. Here we show that Tm4 and Tm5NM1 define separate actin filaments; the former associated with the terminal sarcoplasmic reticulum (SR) and other tubulovesicular structures. In skeletal muscles of Tm5NM1 knockout (KO) mice, Tm4 localization was unchanged, demonstrating the specificity of the membrane association. Tm5NM1 KO muscles exhibit potentiation of T-system depolarization and decreased force rundown with repeated T-tubule depolarizations consistent with altered T-tubule function. These results indicate that a Tm5NM1-defined actin cytoskeleton is required for the normal excitation-contraction coupling in skeletal muscle.
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PMID:Cytoskeletal tropomyosin Tm5NM1 is required for normal excitation-contraction coupling in skeletal muscle. 1900 16