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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Platelet-activating factor (PAF) has been implicated as one of the mediators of cardiac anaphylaxis. This phospholipid has been shown to have numerous effects on a variety of tissues, including the heart. Among these effects are alterations in the resting potential and generation of arrhythmias at very low concentrations. This suggests that PAF may modulate the activity of the background, inwardly-rectifying potassium current (IK1). Thus, the effects of PAF on IK1 were examined at the single channel level. Ventricular cells were isolated from adult guinea pig hearts and single channel currents recorded from cell-attached patches. PAF had substantial effects on the single channel currents at sub-nanomolar concentrations (10(-11) to 10(-10) M). PAF initially caused flickering of the channels, followed by a gradual prolonged depression of channel activity. Since these potassium channels play a major role in determining the resting potential and excitability of the cardiac cell, the effects of PAF on IK1 may play a major role in the deleterious electrophysiological actions of PAF on the heart.
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PMID:Effects of platelet-activating factor on single potassium channel currents in guinea pig ventricular myocytes. 232 95

Effects of Ba on the potassium-related currents were studied on the bullfrog atrial muscle under voltage clamp with double sucrose-gap techniques. Ba, in a dose over 0.1 mM, abolished the anomalous rectification of the membrane by inhibiting the background current which reversed sign nearly at the K equilibrium potential (IK1). Ba, thus reducing the K-depletion current for hyperpolarizations, revealed the presence of funny inward current (If or Ih) in the proper atrial muscle. An increase in [K]0 increased If, and the current showed a threshold at about -80 mV and was saturated at above -160 mV in 5 mM [K]0. The delayed outward current (Ix) for depolarizations was also depressed by Ba. The depression occurred in a voltage- and time-dependent manner, manifesting an unblocking for stronger depolarizations. An analysis of the current tail, however, disclosed that low concentrations of Ba (up to 0.1 mM) inhibited the accumulation component (Ia) of the current without diminishing the next slow component of Ix (Ixs). The remaining Ixs showed a reversal potential of -82 mV, suggesting that this current is largely carried by potassium ions. These data clearly show that in the presence of Ba, If and Ixs can be differentiated from other membrane currents in the frog atrial muscle.
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PMID:Potassium-related membrane currents in the bullfrog atrial muscle differentiated in the presence of barium. 241 Jun 49

We studied the effects of halothane on membrane potentials and ionic currents in single guinea pig atrial and ventricular cells prepared by an enzymatic dispersion procedure. In both atrial and ventricular cells, action potential overshoot and its plateau phase were significantly decreased by halothane (2%) without change in resting potential. However, the duration of the ventricular action potential measured at 90% repolarization was markedly shortened by halothane (2%) (to 60% of control), whereas that of the atrial action potential did not change significantly. Corresponding voltage clamp experiments demonstrated that in atrial cells halothane (2%) significantly depresses the time- and voltage-dependent outward K+ current (IK) (to 46% of control); and that in ventricular cells IK is then nearly absent. In both atrial and ventricular cells halothane had no effect on the inwardly rectifying K+ current (IK1). On the other hand, halothane (2%) decreased the slow inward Ca2+ current (ICa) in both atrial and ventricular cells (to 36% and 29% of control, respectively). The results suggest that the shortened action potential in ventricular cells by halothane may well be responsible for the decrease of the plateau phase resulting from the depression of ICa; and that in atrial cells the depression of IK and ICa by halothane had no significant effect on the duration of action potential.
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PMID:Effects of halothane on membrane ionic currents in guinea pig atrial and ventricular myocytes. 247 84

Primary pharmacological and electrophysiological screening procedures were carried out on the aromatic polycyclic amine 3-hydroxy-4-benzyl-4-azahexacyclo[5.4.1.0(2,6).0(3,10).0(5,9).0(8, 11]- dodecane (NGP 1-01). Effects observed in the isolated guinea-pig atria and ileum were, respectively, reversal of CaCl2 induced positive chronotropy and inotropy and papaverine-like depression of the dose-response curve induced by acetyl choline. Electrophysiological studies using isolated guinea-pig papillary muscle showed a reduction in the action potential (AP) plateau potential and an increase in AP duration with accompanying negative inotropic effects. The calcium-mediated (slow response) AP was completely, but reversibly blocked by NGP 1-01 at concentrations of 5 X 10(-5) M and higher. Experiments on sheep Purkinje fibres strongly supported the finding that NGP 1-01 blocks the slow inward (calcium dependent) current Isi, but also suggested a decrease brought about in an outward current, most probably the background potassium current, IK1.
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PMID:Characterization of NGP 1-01, an aromatic polycyclic amine, as a calcium antagonist. 373 54

The spike peak and after-hyperpolarization of the action potential of bullfrog sympathetic ganglion cells were depressed during the late slow excitatory postsynaptic potential (EPSP). These changes in the action potential were mimicked by luteinizing hormone-releasing hormone (LH-RH), a neurotransmitter candidate for the late slow EPSP. LH-RH (5 microM) suppressed the voltage-dependent K+ currents, both the delayed rectifier K+ current (IK1) and the M current (IK2). It is suggested that the depression of the after-hyperpolarization of the action potential during the late slow EPSP may be due to suppression of IK1 and IK2.
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PMID:Modulation of action potential during the late slow excitatory postsynaptic potential in bullfrog sympathetic ganglia. 636 Mar 8

The mechanism(s) of action of anesthetics on cell membrane ionic currents are not known. To investigate this further the effects of clinically relevant concentrations of ketamine, methohexital, and propofol on the delayed rectifier (IK) and the inward rectifier (IK1) currents of single dispersed guinea pig ventricular myocytes were studied. These voltage-gated currents are major components of cardiac cell electrophysiologic function regulating resting potential and repolarization. Each of the three anesthetics had a distinct spectrum of activity. Ketamine (10(-4) M) decreased IK1 (P < 0.05) but had no effect on IK. Methohexital (10(-4) M) had no significant effect on either current. Propofol (2.8 x 10(-5) M) resulted in significant depression of IK (P < 0.001) but had no effect on IK1. These results suggest that these intravenous anesthetics may have more specific effects on sarcolemma than volatile anesthetics, whose effects may be more generalized membrane effects.
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PMID:Distinctive effects of three intravenous anesthetics on the inward rectifier (IK1) and the delayed rectifier (IK) potassium currents in myocardium: implications for the mechanism of action. 841 22

The intravenous anesthestic thiopental has been previously shown to increase the incidence of ventricular arrhythmias, particularly when combined with epinephrine and halothane. Recent work based on microelectrode and tension measurements has indicated that thiopental may diminish membrane K+ permeability. Utilizing the whole-cell patch-clamp technique, we investigated the effect of thiopental on the current associated with the resting membrane conductance, the anomalous or inward rectifying K+ current (IK1). External application of 30 microM thiopental to frog atrial myocytes resulted in a 56 +/- 2% (mean +/- S.E.M.; n = 12 cells) reduction in the magnitude of IK1 elicited by a hyperpolarization to -110 mV. The outward current component through IK1 channels, evoked by depolarizing voltages above the resting potential, was decreased to same extent. The effect of thiopental on IK1 was concentration-dependent and the time courses of onset and recovery were rapid (tau = 10-14 sec). Ramp command potentials from -120 to +60 mV at a rate of 20 mV/sec revealed that 30 microM thiopental also depressed the delayed outward K+ current by 25 +/- 4% (n = 4). Examination of other barbiturates revealed that the potency in the suppression of IK1 was related to the octanol/water partition coefficient, suggesting a lipophilic site of action. Utilizing guinea pig ventricular myocytes, we observed a similar level of IK1 depression with thiopental, however the rates of onset and recovery were considerably slower than with frog atrial myocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Barbiturate anesthetics depress the resting K+ conductance of myocardium. 847 18

We have examined the effects of propofol and thiopentone on membrane potentials and currents of isolated guineapig ventricular myocytes using the whole-cell patch-clamp technique. After current clamping, propofol at concentrations greater than 0.5 mumol litre-1 shortened the plateau and action potential duration (APD) (P < 0.05). Thiopentone 10 mumol litre-1 prolonged APD (P < 0.05), whereas concentrations of 50 mumol litre-1 or higher decreased plateau height (P < 0.05) and resting membrane potential (RMP) (P < 0.05) with abbreviation of the prolonged APD. With voltage clamping, propofol 1 mumol litre-1 decreased the L-type Ca2+ current (ICa,L) to 88.4% of control (P < 0.01) without affecting the delayed rectifier K+ current (IK) and propofol 10 mumol litre-1 decreased ICa,L and IK to 75.0% (P < 0.01) and 78.4% (P < 0.01), respectively, with no effect on the inward rectifier K+ current (IK1). Thiopentone 10 mumol litre-1 decreased ICa,L to 88.5% (P < 0.01) and IK to 78.3% (P < 0.05), while thiopentone 100 mumol litre-1 depressed ICa,L to 82.8% (P < 0.01), IK to 27.0% (P < 0.01) and IK1 to 67.3% (P < 0.05). These results indicated that propofol, at concentrations greater than those that are clinically relevant, shortened APD mainly by suppression of ICa,L, and the biphasic effects on APD by thiopentone were caused by depression of IK, and concomitant suppression of ICa,L and IK1 at higher concentrations. The distinct cardiodepressant effects of propofol and thiopentone may be, at least in part, attributed to different actions on membrane Ca2+ and K+ currents.
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PMID:Comparative actions of propofol and thiopentone on cell membranes of isolated guineapig ventricular myocytes. 894 38

Effects of extracellular applications of different types of Ca2+ channel blocking agents (Mn2+, verapamil, and nisoldipine) on action-potential duration and membrane currents were studied by the whole-cell patch-clamp technique in guinea pig ventricular myocytes. Low concentrations of Mn2+ (1 mM) and verapamil (1 microM) prolonged action-potential duration at 90% repolarization (APD90) with a suppressed plateau phase. Increases in Mn2+ (5 mM) and verapamil (5 microM) shortened APD90 with a further depression of the plateau. Nisoldipine (0.2-1 microM) shortened APD90 without lengthening it. Applications of Mn2+ and verapamil suppressed amplitudes of the L-type Ca2+ current (ICa), the delayed outward K+ current (IK), and the inward rectifier K+ current (IK1). Furthermore, the ratios of ICa:IK inhibition were similar by low and high concentrations of Mn2+ and verapamil. Nisoldipine selectively suppressed ICa without effect on IK and IK1. A low concentration (1 mM) of Mn2+ not only decreased the peak amplitude of ICa but also delayed its decay time course, which caused an increase in late ICa amplitude at the end of a 200-ms depolarizing pulse. Both verapamil and nisoldipine suppressed peak ICa without affecting its decay. Whereas Mn2+ suppressed IBa without changing its decay time course, verapamil and nisoldipine speeded up the IBa decay with suppressed amplitude of IBa. We conclude that different types of Ca2+ channel blocking agents (Mn2+, verapamil, and nisoldipine) diversely modulate APD because of their multiple modes of actions on ICa and IK.
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PMID:Multiple modulations of action potential duration by different calcium channel blocking agents in guinea pig ventricular myocytes. 933 9

Changes in ionic currents through ion channels of the myocardial cell membrane have to be regarded as main cause of cardiac arrhythmias. Three basic arrhythmogenic mechanisms are responsible for the initiation of tachyarrhythmias: 1. The disturbance of normal automaticity in cardiac pacemaker cells dependent on the currents If, ICa-L, ICa-T or IK-ACh,Ado and the occurrence of abnormal automaticity in atrial and ventricular working myocardium based on the currents ICa-L, INa, IK, IK1 or IK-ACh,Ado. 2. Triggered activity which may be recognized by the appearance of early (EAD) or late afterdepolarizations (LAD). EAD are mainly due to inhibition of the outward currents IKr and IKs and are favoured by an increase in the inward currents INa and ICa-L, respectively. Typical arrhythmias are torsade de pointes occurring during treatment with K(+)-channel inhibitors (e.g. sotalol) or in patients with QT-syndrome. LAD may be observed during Ca(2+)-overload of the myocardial cell (digitalis intoxication, catecholamines) and are based on the transient inward current Iti, which is build up by the participation of the currents INa/Ca, INS and ICa-L. 3. Reentry mechanisms are the most frequent cause of tachyarrhythmias. They originate in an anatomically defined excitation circle with unidirectional block. Na(+)- and Ca(2+)-channel dependent disturbances of conduction with long excitable gap may be distinguished from Na(+)-channel dependent disturbances of conduction and refractory period with short excitable gap. Interruption of reentry is possible in the first case by depression of conduction and excitability (Na(+)- or Ca(2+)-channel blockers), in the second case by increase in refractory period (K(+)- or Na(+)-channel blockers).
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PMID:[Ion channels and arrhythmias]. 1081 Jul 80


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