Voltage Clamp Studies on the Slow Inward Current during the Excitation ofNitellopsis obtusa

1980 ◽  
Vol 31 (2) ◽  
pp. 589-595 ◽  
Author(s):  
M. GYENES ◽  
A. A. BULYCHEV ◽  
G. A. KURELLA
Keyword(s):  
Voltage Clamp ◽  
Slow Inward Current ◽  
Inward Current

The toxic effects of ouabain: A voltage-clamp study

1982 ◽  
Vol 60 (9) ◽  
pp. 1153-1159 ◽  
Author(s):  
Y. Deslauriers ◽  
E. Ruiz-Ceretti ◽  
O. F. Schanne ◽  
M. D. Payet
Keyword(s):  
Action Potential ◽  
Voltage Clamp ◽  
Sodium Current ◽  
Negative Inotropic Effect ◽  
Slow Inward Current ◽  
Inward Current ◽  
Toxic Concentration ◽  
Voltage Curve ◽  
Current Voltage Curve ◽  
High Concentrations

The electrophysiologic effects of a toxic concentration of ouabain (10−5 M) were studied in frog atrial trabeculae. The toxic concentration was determined by the appearance of a negative inotropic effect and an increase in basal tension. Current- and voltage-clamp measurements were performed. Ouabain did not alter the passive electrical properties of the preparation. Under current-clamp conditions the membrane depolarized and the action potential amplitude as well as its maximum rate of rise decreased. The current–voltage curve for the fast inward current was shifted toward more positive potentials and the maximum sodium current decreased. The maximum sodium conductance was also reduced. The process of reactivation of the fast inward current was accelerated. The slow inward current and the maximum slow conductance also decreased under ouabain. These effects could explain the negative inotropic action of high concentrations of glycosides, as well as the action potential changes observed by several investigators. They also help to understand the arrhythmogenic effects of high concentrations of digitalis.

Tl+-Ions: Comparison of the Effects on the Slow Inward Current and Contractility of Ventricular Tissues

1982 ◽  
Vol 37 (10) ◽  
pp. 1015-1022 ◽  
Author(s):  
J. Wiemer ◽  
R. Ziskoven ◽  
C. Achenbach
Keyword(s):  
Voltage Clamp ◽  
Current System ◽  
Slow Inward Current ◽  
Initial Increase ◽  
Purkinje Fibres ◽  
Cardiac Tissues ◽  
Inward Current ◽  
Current Voltage ◽  
Apparent Relationship ◽  
Time Courses

To conclude our investigation of thallium effects on cardiac tissues, we studied the slow inward current of sheep cardiac Purkinje fibres exposed to 10-7 to 10-5 ᴍ Tl+ for extended periods of up to 80 min. Our previous results had suggested a possible involvement of the slow inward current during thallium intoxication: a) the modification of contractility staircases observed during thallium exposure, b) action potential recordings of ventricular muscle, c) changes in spontaneous beating in sino-atrial preparations. The thallium levels chosen were between those yielding strong positive inotropic transients and those producing a marked long­term decay of contraction force.The slow inward current was measured using a conventional two-microelectrode-technique and the standard voltage clamp protocol for this current system. The experimental work was restricted to the determination of d∞, the kinetics of activation of the slow inward current and of īsi, the current voltage relation of the current system. This was necessary since the effects of thallium were known to be short-lived and therefore frequent repeat runs of the voltage clamp program had to be performed in order to obtain the time courses of possible transient changes.The results showed that the slow inward current was first increased and then declined at the low concentration of 10-7 ᴍ Tl+. At 10-5 m Tl+ the initial increase was smaller, whereas the decay of the slow inward current proceeded to lower values. Comparison with contractility measure­ments at the same concentrations of thallium showed a distinct parallelism between changes of the slow inward current and myocardial contractility. Despite this apparent relationship, we do not conclude that the contractile events are primarily a result of changes of the slow inward current, since thallium does not seem to specifically alter the parameters of the slow inward current at the membrane level.

Mechanism of block by ZD 7288 of the hyperpolarization-activated inward rectifying current in guinea pig substantia nigra neurons in vitro

1995 ◽  
Vol 74 (6) ◽  
pp. 2366-2378 ◽  
Author(s):  
N. C. Harris ◽  
A. Constanti
Keyword(s):  
Substantia Nigra ◽  
Guinea Pig ◽  
Voltage Clamp ◽  
Time Constant ◽  
Slow Inward Current ◽  
Current Clamp ◽  
Inward Current ◽  
Electrotonic Potential ◽  
Zd 7288

1. The effects of the novel bradycardic agent 4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyrimidinium chloride (ZD 7288) (Zeneca) were investigated on the hyperpolarization-activated cationic current (Ih) in guinea pig substantia nigra pars compacta neurons in vitro, using a single-microelectrode current-clamp/voltage-clamp technique. 2. Under current-clamp conditions, injection of large negative current pulses (0.1-0.5 nA, 400 ms) evoked a slow depolarizing "sag" in the electrotonic potential due to activation of the slow inward (anomalous) rectifier. In voltage-clamp recordings, hyperpolarizing voltage steps from a holding potential of -60 mV (close to resting potential) elicited slow inward current relaxations with kinetic properties similar to those seen for other neuronal Ihs. 3. ZD 7288 (10-100 microM) produced a consistent abolition of the electrotonic potential sag with no effect on membrane potential or spike properties. Under voltage clamp, Ih amplitude was clearly reduced in a time- and concentration-dependent manner (apparent half-maximum blocking concentration = 2 microM); full block of Ih was typically achieved after 10-15 min of exposure to 50 microM ZD 7288, with no significant recovery observed after 1 h of washing. 4. A similar (although more rapid) block of Ih was seen after application of 3-5 mM Cs+ (partially reversible after 30 min of washing). 5. Partial block of Ih by 10 microM ZD 7288 was accompanied by a reduction in the maximum amplitude of the Ih activation curve, a small negative shift in its position on the voltage axis, and a linearization of the steady-state current-voltage relationship. The estimated Ih reversal potential, however, remained unaffected. 6. In 10 microM ZD 7288, the time course of Ih activation and deactivation was significantly slowed (within the range of -70 to -120 mV for the activation time constant and -70 to -90 mV for the inactivation time constant). 7. Blockade of Ih by ZD 7288 or Cs+ was independent of prior Ih activation (i.e., non-use dependent). 8. Intracellular loading with ZD 7288 also abolished the sag in the electrotonic voltage response and Ih relaxations, suggesting an intracellular site of action. By contrast, intracellular Cs+ had no effect on Ih properties. 9. Block of Ih by ZD 7288 (but not Cs+) was relieved by prolonged cell hyperpolarization, manifested as a slowly developing (half-time approximately 20 s) inward current at a holding potential of -100 mV. 10. We propose that ZD 7288, when applied externally, may behave as a "lipophilic" quaternary cation, capable of passing into the cell interior to block Ih channels in their closed state; this compound may thus prove a useful research tool, in place of Cs+, for studying the properties and significance of Ih currents in controlling neuronal function.

Histamine depolarizes cholinergic septal neurons

1996 ◽  
Vol 75 (2) ◽  
pp. 707-714 ◽  
Author(s):  
N. Gorelova ◽  
P. B. Reiner
Keyword(s):  
Voltage Clamp ◽  
Receptor Agonist ◽  
Potassium Conductance ◽  
Input Resistance ◽  
Slow Inward Current ◽  
H1 Receptor ◽  
Inward Current ◽  
H2 Receptor ◽  
Inwardly Rectifying ◽  
Slow Depolarization

1. Bath application of 10 microM histamine (HA) resulted in a depolarization or inward current in 58/59 cholinergic neurons located in the medial septum and nucleus of the diagonal band of Broca (MS/DBB) in a slice preparation of rat brain. 2. In bridge mode, the histamine-induced depolarization consisted of both fast and slow phases; inward currents that followed the comparable time course were observed under voltage-clamp conditions. The fast depolarization was associated with variable changes in input resistance, while the slow depolarization always was associated with an increase in input resistance. 3. Both fast and slow responses persisted in the presence of tetrodotoxin (TTX), but only the fast response persisted when transmitter release was abolished by bathing the slice in either a low-Ca(2+)-, high-Mg(2+)-containing medium or one containing Cd2+. 4. When ramp voltage-clamp commands were applied during the fast depolarization, the resultant current-voltage (I-V) curves did not intersect over the range of membrane potentials from -130 to -30 mV. Ionic substitution experiments suggested that the bulk of the ionic current flowing during the fast depolarization was carried by sodium ions. 5. The I-V characteristics of the slow inward current identified it as a reduction in an inwardly rectifying potassium conductance. 6. The fast depolarization was significantly reduced by the H1 receptor antagonists pyrilamine and promethazine, but not by the H2 receptor antagonist cimetidine. Neither the H2 receptor agonist impromidine nor the H3 receptor agonist R-alpha-methylhistamine mimicked the response to HA. None of the agonists or antagonists had any observable effect upon the slow depolarization. 7. We conclude that HA directly depolarizes cholinergic MS/DBB neurons by acting as an H1 receptor, which primarily couples to an increase in a TTX-insensitive Na+ conductance. Additionally, HA evokes a slow depolarization mediated by a decrease in an inwardly rectifying potassium conductance but is not generated by activation of classically defined HA receptor subtypes.

Effects of manganese chloride on the outward currents in frog atrial trabeculae

1985 ◽  
Vol 63 (9) ◽  
pp. 1065-1069 ◽  
Author(s):  
Julio L. Alvarez ◽  
Miguel Garcia ◽  
Francisco R. Dorticós ◽  
Jesús A. Morlans
Keyword(s):  
Voltage Clamp ◽  
Outward Current ◽  
Manganese Chloride ◽  
Exchange Current ◽  
Time Dependent ◽  
Slow Inward Current ◽  
Background Current ◽  
Inward Current ◽  
Atrial Muscle ◽  
Outward Currents

The effects of MnCl2 on outward currents in frog atrial muscle were investigated under voltage-clamp conditions. MnCl2 (3 mmol/L), which completely abolished the slow inward current, produced a decrease in the outward background current (Ib) at potentials positive to −50 mV. The delayed outward current (Ix, time dependent) was not altered by Mn. "Isochronic activation curves" for Ix and decay of current tails at −40 mV remained unaffected after Mn. Effects on Ib probably reflect a decrease in [Formula: see text] related to the decrease in Ca influx as well as a reduction in the Na–Ca exchange current.

Calcium-dependent plateau potentials in a crab stomatogastric ganglion motor neuron. II. Calcium-activated slow inward current

1995 ◽  
Vol 74 (5) ◽  
pp. 1938-1946 ◽  
Author(s):  
B. Zhang ◽  
J. F. Wootton ◽  
R. M. Harris-Warrick
Keyword(s):  
Motor Neuron ◽  
Voltage Clamp ◽  
Physiological Role ◽  
Reversal Potential ◽  
Stomatogastric Ganglion ◽  
Slow Inward Current ◽  
Inward Current ◽  
Tail Current ◽  
Plateau Potential ◽  
Voltage Dependent

1. Using intracellular recording and voltage-clamp techniques, we examined the biophysical properties of a Ca(2+)-activated slow inward current and its physiological role in plateau potential generation in the dorsal gastric (DG) motor neuron of the stomatogastric ganglion in the crab, Cancer borealis. 2. As shown in the accompanying paper, a brief puff of serotonin (5-HT) evoked a plateau potential in the DG neuron. Intracellular loading of the Ca2+ chelator ethylene glycol-bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) prevented 5-HT from evoking a plateau potential. On the contrary, rapid increase of intracellular Ca2+ by photolysis of caged-Ca2+ (bound to DM-nitrophen) evoked a plateau response in DG bathed in normal saline. 3. Extracellular tetrodotoxin (TTX), tetraethylammonium (TEA), 4-aminopyridine (4-AP), and Cs+ and intracellular iontophoresis of Cs+ were used to block voltage-dependent INa, IK, and Ih. Under these conditions we voltage clamped DG using two electrodes and isolated a long-lasting tail current after a short depolarization of the cell. 4. The reversal potential of the slow tail current was extrapolated to be -27 +/- 3.5 (SE) mV. Na+ substitutions with choline+, tris(hydroxymethyl)aminomethane+ (Tris+) or n-methyl-glucamine+ (NMG+) did not significantly affect the reversal potential or the amplitude. 5. The slow tail current was Ca2+ dependent. It was reduced or abolished by the Ca2+ channel blocker Co2+, intracellular injection of EGTA, and by Ba2+ replacement of Ca2+ as the charge carrier. The activation and deactivation of this current do not show an apparent dependence on voltage. 6. When the voltage-dependent Na+, K+, and Ca2+ channels were blocked, a brief puff of caffeine evoked a slow depolarization. In voltage clamp, caffeine evoked a slow inward current with an apparent conductance increase. This current was reduced by intracellular EGTA. The current-voltage (I-V) relationship of the caffeine-evoked current was linear with a reversal potential of -25 +/- 4.8 mV. This was not statistically different from the reversal potential of the depolarization-evoked tail current. 7. 5-HT enhanced the depolarization-evoked slow tail current but had no effect on the caffeine-evoked slow inward current. 8. We conclude that the slow tail current is a Ca(2+)-activated nonselective current, similar to the Ca(2+)-activated nonspecific cation currents described in other preparations. This current appears to play an important role in plateau generation and maintenance in DG. 5-HT has no direct effect on the properties of this current, but it indirectly enhances the current through an increase of voltage-dependent Ca2+ current.

Voltage clamp discloses slow inward current in hippocampal burst-firing neurones

Nature ◽  
1980 ◽  
Vol 286 (5771) ◽  
pp. 391-393 ◽  
Author(s):  
Daniel Johnston ◽  
John J. Hablitz ◽  
Wilkie A. Wilson
Keyword(s):  
Voltage Clamp ◽  
Burst Firing ◽  
Slow Inward Current ◽  
Inward Current

scholarly journals Two Inward Currents in Frog Atrial Muscle

1971 ◽  
Vol 58 (5) ◽  
pp. 523-543 ◽  
Author(s):  
Merrill Tarr
Keyword(s):  
Action Potential ◽  
Voltage Clamp ◽  
Ionic Currents ◽  
Ringer Solution ◽  
Slow Inward Current ◽  
Slow Phase ◽  
Free Solution ◽  
Rapid Phase ◽  
Inward Current ◽  
Atrial Tissue

The double sucrose-gap voltage-clamp technique was applied to frog atrial tissue to investigate the ionic currents responsible for the action potential in this tissue. Membrane depolarization elicited two distinct components of inward current when the test node was exposed to normal Ringer solution: a fast inward current and a slow inward current. The fast inward current appeared to be carried by sodium ions, since it was rapidly abolished by exposure of the fiber to Na+-free solution or tetrodotoxin but persisted on exposure to Ca++-free solution. In contrast, in the majority of the preparations the slow inward current appeared to be primarily carried by calcium ions, since it was abolished on exposure of the fiber to Ca++-free solution but persisted on exposure to Na+-free solution. Action potential data supported the voltage-clamp findings. The normal action potential shows two distinct components in the upstroke phase: an initial rapid phase of depolarization followed by a slower phase of depolarization reaching the peak of the action potential. Abolition of the fast inward current resulted in abolition of the initial rapid phase of depolarization. Abolition of the slow inward current resulted in abolition of the slow phase of depolarization. These data support the hypothesis that two distinct and different ionic mechanisms contribute to the upstroke phase of the action potential in frog atrial tissue.

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