Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Ventricular myocytes were isolated by enzymatic dispersion of adult rabbit hearts, and voltage clamped using the whole-cell variation of the patch clamp technique. Experiments were carried out at either 35 degrees C or room temperature (21-23 degrees C). 2. In the presence of 10(-3) M-4-aminopyridine to block the transient outward K+ current, and 10(-6) M-propranolol to block beta-adrenoceptors, the alpha 1-adrenergic agonist methoxamine produced action potential prolongation, and a small depolarization of the diastolic membrane potential. Under voltage clamp conditions, methoxamine decreased the magnitude of the inward rectifier K+ current, IK1, in both the inward and outward directions. This effect was dose dependent (10(-5)-10(-3) M) and fully reversible upon wash-out of the agonist. 3. The neurotransmitter noradrenaline (10(-6)-2 x 10(-5) M), in the presence of propranolol (10(-6) M), also reduced IK1 in ventricular cells, and this effect was blocked by the specific alpha 1-adrenoceptor antagonist prazosin. 4. The alpha 1-adrenoceptor-mediated decrease in IK1 in ventricular myocytes was not affected by pre-incubation of the cells with 0.5 micrograms/ml pertussis toxin (8-10 h, 30-32 degrees C). This result suggests that in rabbit ventricular cells, the alpha 1-modulation of IK1 occurs via a pertussis toxin-insensitive guanine nucleotide-binding regulatory protein. 5. These observations demonstrate that IK1 in ventricular myocytes can be modulated by cardiac alpha 1-adrenoceptors. The resulting changes in action potential repolarization and diastolic membrane potential may have significant effects on cardiac performance.
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PMID:Alpha 1-adrenoceptors reduce background K+ current in rabbit ventricular myocytes. 166 3

Using the patch-clamp technique, we studied regulation of potassium channels by G protein activators in the histamine-secreting rat basophilic leukemia (RBL-2H3) cell line. These cells normally express inward rectifier K+ channels, with a macroscopic whole-cell conductance in normal Ringer ranging from 1 to 16 nS/cell. This conductance is stabilized by including ATP or GTP in the pipette solution. Intracellular dialysis with any of three different activators of G proteins (GTP gamma S, GppNHp, or AlF-4) completely inhibited the inward rectifier K+ conductance with a half-time for decline averaging approximately 300 s after "break-in" to achieve whole-cell recording. In addition, with a half-time averaging approximately 200 s, G protein activators induced the appearance of a novel time-independent outwardly rectifying K+ conductance, which reached a maximum of 1-14 nS. The induced K+ channels are distinct from inward rectifier channels, having a smaller single-channel conductance of approximately 8 pS in symmetrical 160 mM K+, and being more sensitive to block by quinidine, but less sensitive to block by Ba2+. The induced K+ channels were also highly permeable to Rb+ but not to Na+ or Cs+. The current was not activated by the second messengers Ca2+, inositol 1,4,5-trisphosphate, inositol 1,3,4,5-tetrakisphosphate, or by cyclic AMP-dependent phosphorylation. Pretreatment of cells with pertussis toxin (0.1 microgram/ml for 12-13 h) prevented this current's induction both by guanine nucleotides and aluminum fluoride, but had no effect on the decrease in inward rectifier conductance. Since GTP gamma S is known to stimulate secretion from patch-clamped rat peritoneal mast cells, it is conceivable that K+ channels become inserted into the plasma membrane from secretory granules. However, total membrane capacitance remained nearly constant during appearance of the K+ channels, suggesting that secretion induced by GTP gamma S was minimal. Furthermore, pertussis toxin had no effect on secretion triggered by antigen, and triggering of secretion before electrical recording failed to induce the outward K+ current. Finally, GTP gamma S activated the K+ channel in excised inside-out patches of membrane. We conclude that two different GTP-binding proteins differentially regulate two subsets of K+ channels, causing the inward rectifier to close and a novel K+ channel to open when activated.
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PMID:G protein control of potassium channel activity in a mast cell line. 210 71

Isolated, cultured arterial endothelial cells express an acetylcholine (ACh)-activated K+ current in addition to an inward rectifier current whose conductance is unaffected by ACh. The cholinergic K+ current is specifically blocked by atropine (1 microM) and shows single saturation kinetics with ACh (half-maximal stimulation 51 nM ACh). Unlike the cardiac muscarinic receptor-gated K+ channel, its stimulation appears independent of a pertussis toxin-sensitive GTP-binding protein. Activation of the endothelial muscarinic K+ current resulting in hyperpolarization may represent an initial component of the vasodilatory effect of ACh.
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PMID:Muscarinic-activated K+ current in bovine aortic endothelial cells. 245 60

Galanin inhibits depolarization-induced dopamine release from chromaffin cells. In excised membrane patches, galanin induced openings of a 36 pS, inwardly rectifying potassium channel. Galanin activation of this K+ channel was blocked by pretreatment with pertussis toxin. Galanin is without effect on L-type Ca2+ channels.
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PMID:Galanin inhibits dopamine secretion and activates a potassium channel in pheochromocytoma cells. 247 Apr 71

The cellular actions of 5-hydroxytryptamine (5-HT) on adult and neonatal rat central neurones have been investigated in detail using a combination of in vitro slice and dissociated neurone preparations. Patch-clamp recordings from acutely dissociated adult rat dorsal raphe neurones confirm data obtained using conventional slice preparations that 5-HT activates an inwardly rectifying potassium channel through a 5-HT1A receptor leading to hyperpolarization of the cell. Single-channel recordings indicate that this pathway requires only the involvement of a pertussis toxin-sensitive G-protein. Adult rat facial motoneurones in conventional slices are depolarized by 5-HT through a combination of mechanisms, closure of potassium channels and enhancement of the hyperpolarization-activated, cationic current, IH. Distinct receptors appear to mediate these two actions. Both mechanisms are present in visually indentified neonatal rat facial motoneurones in thin brain slices. Whole-cell patch-clamp recordings show the action of 5-HT on IH to mediate a caesium-sensitive inward current which can be mimicked by the adenylate cyclase activator, forskolin. The experimental data illustrate how a range of complimentary in vitro electrophysiological techniques can be employed to unravel neurotransmitter mechanisms and pharmacology.
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PMID:The use of brain slices and dissociated neurones to explore the multiplicity of actions of 5-HT in the central nervous system. 747 48

In locus coeruleus neurons, substance P (SP) suppresses an inwardly rectifying K+ current via a pertussis toxin-insensitive guanine nucleotide binding protein (G protein; GnonPTX), whereas somatostatin (SOM) or [Met]enkephalin (MENK) enhances it via a pertussis toxin-sensitive G protein (GPTX). The interaction of the SP and the SOM (or MENK) effects was studied in cultured locus coeruleus neurons. In neurons loaded with guanosine 5'-[gamma-thio]triphosphate (GTP[gamma S]), application of SOM (or MENK) evoked a persistent increase in the inward rectifier K+ conductance. A subsequent application of SP suppressed this conductance to a level less than that before the SOM (or MENK) application; the final conductance level was independent of the magnitude of the SOM (or MENK) response. This suppression by SP was persistent, and a subsequent SOM (or MENK) application did not reverse it. When SP was applied to GTP[gamma S]-loaded cells first, subsequent SOM elicited only a small response. In GTP-loaded neurons, application of SP temporarily suppressed the subsequent SOM- (or MENK)-induced conductance increase. These results suggest that the same inward rectifier molecule that responds to an opening signal from GPTX also responds to a closing signal from GnonPTX. The closing signal is stronger than the opening signal.
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PMID:Opposing mechanisms of regulation of a G-protein-coupled inward rectifier K+ channel in rat brain neurons. 753 96

1. The potassium currents evoked in isolated and identified neurones of molluscan pedal ganglia by either glutamate, dopamine or the muscarinic agonist F-2268 were investigated using voltage and patch clamp techniques. 2. Potassium currents induced by either dopamine or F-2268 could be blocked by pertussis toxin, as well as by a prolonged intracellular injection of the G protein inhibitor, GDP-beta-S. Loading the neurones with the G protein activator, GppNHp, on the other hand, induced a potassium current. This current was not additive to the currents evoked by agonist application. 3. Intracellular injection of the calcium buffer BAPTA failed to affect any of the agonist-induced currents, although it effectively blocked the after-hyperpolarization following directly evoked action potentials. 4. The activity of the potassium channels seen in cell-attached patches was greatly enhanced by application to the bath of either glutamate, dopamine, or F-2268. 5. The only effect of an addition of agonists to the bath was to increase the open probability (Po) of the K+ channel already active in the control conditions. The identity of the spontaneously active and agonist-activated channels was concluded from the identity of their channel conductances, rectification properties and current amplitudes. 6. Phorbol-12,13-dibutyrate, when applied to the bath, induced an increase in open time and caused an increase in Po, as did the agonists. Staurosporine completely prevented changes of Po induced by the phorbol ester but not those induced by the agonists. 7. The same inwardly rectifying potassium channel may be opened by both the receptor-linked G protein (with glutamate, dopamine, F-2268) and by protein kinase C (with phorbol ester) activation. 8. Strong evidence was obtained against the involvement of any known secondary messenger systems (formation of nucleotides, phosphoinositide turnover and subsequent activation of protein kinase C, formation of nitric oxide, metabolism of arachidonic acid) in the transduction mechanism of F-2268-, dopamine- and glutamate-induced responses. 9. Since none of the known secondary messenger systems seems to affect the activation by agonists applied to receptors outside the patch of channels located under the patch electrode, it appears that some as yet undescribed linking system must exist that could connect the spatially separated receptor-G protein complex and the potassium channel.
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PMID:Activation of a common potassium channel in molluscan neurones by glutamate, dopamine and muscarinic agonist. 790 68

Acetylcholine released during parasympathetic stimulation of the vagal nerve slows the heart rate through the activation of muscarinic receptors and subsequent opening of an inwardly rectifying potassium channel. The activation of these muscarinic potassium channels is mediated by a pertussis toxin-sensitive heterotrimeric GTP-binding protein (G protein). It has not been resolved whether exogenously applied G alpha or G beta gamma, or both, activate the channel. Using a heterologous expression system, we have tested the ability of different G protein subunits to activate the cloned muscarinic potassium channel, GIRK1. We report here that coexpression of GIRK1 with G beta gamma but not G alpha beta gamma in Xenopus oocytes results in channel activity that persists in the absence of cytoplasmic GTP. This activity is reduced by fusion proteins of the beta-adrenergic receptor kinase and of recombinant G alpha i-GDP, both of which are known to interact with G beta gamma. Moreover, application of recombinant G beta gamma, but not G alpha i-GTP-gamma S, activates GIRK1 channels. Thus G beta gamma appears to be sufficient for the activation of GIRK1 muscarinic potassium channels.
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PMID:Activation of the cloned muscarinic potassium channel by G protein beta gamma subunits. 802 83

Human D2, D3, D4 and dopamine receptors were individually coexpressed in Xenopus oocytes with a G protein-regulated inwardly rectifying potassium channel (GIRK1). At -100 mV in 96 mM potassium, dopamine (0.1-100 nM) evoked an inward current; the current showed inward rectification, reversed polarity at 0 mV, and was blocked by barium (50% inhibition by 10 microM). The concentrations of dopamine activating 50% of the maximal current (EC50) were not different (2-4 nM) for D2, D3, and D4 receptors, but the maximal current was 3-fold larger for D2 and D4 than for D3 receptors. Dopamine evoked reproducible inward currents at D2 and D4 receptors when applied repeatedly, but second responses could not be observed in oocytes expressing D3 receptors. 7-Hydroxy-N,N-di-n-propyl-2-aminotetralin mimicked the effect of dopamine (EC50 of approximately 2, approximately 3, and approximately 19 nM at D2, D3, and D4, respectively). (-) Sulpiride reversibly blocked the dopamine-induced current with IC50 values of 5, 300, and 2000 nM for D2, D3, and D4 receptors, respectively. Dopamine was ineffective in oocytes injected 2 hr previously with pertussis toxin. We concluded that all three D2-like dopamine receptors share the potential to activate inwardly rectifying potassium channels.
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PMID:D2, D3, and D4 dopamine receptors couple to G protein-regulated potassium channels in Xenopus oocytes. 860 93

Receptor-mediated activation of a G-protein-coupled inwardly rectifying potassium channel (GIRK) is a common mechanism for synaptic modulation in the CNS. However, evidence for metabotropic glutamate receptor (mGluR) activation of GIRK is virtually nonexistent, despite the widespread and overlapping distribution of these proteins. We examined this apparent paradox by coexpressing mGluRs 1a, 2, and 7 with the GIRK subunits Kir3.1 and Kir3.4 in Xenopus oocytes. Functional expression of GIRK was confirmed by coexpression with the D2 dopamine receptor that is known to activate GIRK in neurons. Agonist activation of each of the three mGluRs evoked inward potassium currents in symmetrical KCI solutions. The current amplitudes evoked by mGluR1a, mGluR2, and D2 were comparable, whereas mGluR7 currents were somewhat smaller. mGluR1a-evoked GIRK currents were not blocked in BAPTA-treated oocytes, demonstrating that GIRK activation was distinct from phospholipase C-mediated activation of the endogenous calcium-dependent chloride current (lCaCl). Pertussis toxin (PTX) treatment significantly reduced both the mGluR and D2 receptor-evoked GIRK currents. In oocytes in which mGluR2 and D2 were coexpressed, activation of mGluR2 occluded additional D2 receptor current, indicating that mGluR2 and D2 receptor coupling to GIRK involves a common G-protein. The efficient coupling of mGluRs to GIRK in oocytes suggests either that mGluR activation of GIRK has been overlooked in neurons or possibly that mGluRs are excluded from GIRK-containing microdomains.
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PMID:Metabotropic glutamate receptors activate G-protein-coupled inwardly rectifying potassium channels in Xenopus oocytes. 881 80


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