Gene/Protein Disease Symptom Drug Enzyme Compound
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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

We have studied the effects of activated G proteins (Gs alpha and Gi1 alpha), adenosine 3',5'-cyclic monophosphate-dependent protein kinase (PKA), and okadaic acid on L-type Ca channels incorporated from porcine ventricular sarcolemma into planar lipid bilayers. Channel activity evoked by membrane depolarizations diminished to extremely low levels within 2 min of incorporation (channel "rundown"). When Gs alpha [activated with guanosine 5'-O-(3-thiotriphosphate)] was present in the intracellular chamber, the initial level of channel activity was increased and rundown was delayed, so that channel activity was sustained for longer times after incorporation. The effect was specific for activated Gs alpha; activated Gi1 alpha, heat-denatured, activated Gs alpha, and unactivated Gs alpha did not augment channel activity. Activated Gi1 alpha inhibited the stimulation of Ca channel activity by Gs alpha. Treatment of the sarcolemmal membranes with PKA and Mg-ATP also increased the initial channel open probability and delayed their rundown. Addition of intracellular Gs alpha to PKA-treated channels increased the initial level of activity above that seen with PKA or Gs alpha alone, suggesting different nonocclusive pathways for the channel stimulation. This was also supported by the observation that activated Gi1 alpha had no effect on PKA-treated channels. Okadaic acid (100 nM) increased the level of Ca channel activity, suggesting that dephosphorylation by endogenous phosphatases participated in the downregulation of the channels in cell-free membranes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of cardiac L-type Ca channels in planar lipid bilayers by G proteins and protein phosphorylation. 839 96

Locus coeruleus (LC) is the significant nucleus for consciousness and it is sensitive to metabolic inhibition. We investigated the effects of a metabolic inhibitor sodium cyanide (NaCN) on the rat dissociated LC neurons using nystatin-perforated patch recordings. Under voltage-clamp (VH=-40 mV), application of NaCN evoked outward currents composed of ATP-sensitive and Ca2+-dependent K+ channel currents (IKATP and IKCa2+). Onset of IKATP was faster than that of IKCa2+. Prolonged application of NaCN brought IKATP rundown but not IKCa2+ rundown. Okadaic acid prevented IKATP rundown, indicating that KATP channels are deactivated by dephosphorylation with protein phosphatase.
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PMID:ATP-sensitive and Ca2+-activated K+ channel activities in the rat locus coeruleus neurons during metabolic inhibition. 1032 Jul 42