Inhibition of the slow inward current and the time-dependent outward current of mammalian ventricular muscle by gentamicin

1982 ◽  
Vol 394 (3) ◽  
pp. 243-249 ◽  
Author(s):  
N. Hino ◽  
R. Ochi ◽  
T. Yanagisawa
Keyword(s):  
Outward Current ◽  
Time Dependent ◽  
Slow Inward Current ◽  
Ventricular Muscle ◽  
Inward Current

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.

scholarly journals On the ionic mechanism underlying adrenergic-cholinergic antagonism in ventricular muscle.

1982 ◽  
Vol 79 (1) ◽  
pp. 69-86 ◽  
Author(s):  
I Josephson ◽  
N Sperelakis
Keyword(s):  
Reversal Potential ◽  
Outward Current ◽  
Cyclic Adenosine Monophosphate ◽  
Negative Inotropic Effect ◽  
Adenosine Monophosphate ◽  
Slow Inward Current ◽  
Ventricular Muscle ◽  
Adrenergic Stimulation ◽  
Inward Current ◽  
K Current

In atrial muscle, acetylcholine (ACh) decreases the slow inward current (Isi) and increases the time-independent outward K+ current. However, in ventricular muscle, ACh produces a marked negative inotropic effect only in the presence of positive inotropic agents that elevate cyclic adenosine monophosphate (AMP). A two-microelectrode voltage-clamp method was used on cultured reaggregates of cells from 16--20-d-old embryonic chick ventricles to determine the effects of ACh on Isi and outward current during beta-adrenergic stimulation. Only double penetrations displaying low-resistance coupling were voltage-clamped. Cultured reaggregates are advantageous because their small size (50--250 microns) permits better control of membrane potential and adequate space clamp. Tetrodotoxin (10(-6) M) and a holding potential of --50 to --40 mV were used to eliminate the fast Na+ current. Depolarizing voltage steps above --40 mV caused a slow inward current to flow that was sensitive to changes in [Ca]o and was depressed by verapamil (10(-6) M). Maximal Isi was obtained at --10 mV and the reversal potential was about +25 mV. Isoproterenol (10(-6) M) increased Isi at all clamp potentials. Subsequent addition of ACh (10(-6) M) rapidly reduced Isi to control values (before isoproterenol) without a significant effect on the net outward current measured at 300 ms. The effects of ACh were reversed by muscarinic blockade with atropine (5 X 10(-6) M). We conclude that the anti-adrenergic effects of ACh in ventricular muscle are mediated by a reduction in Ca2+ influx during excitation.

Slow inward current may produce many results attributed to IX1 in cardiac Purkinje fibers

1985 ◽  
Vol 249 (1) ◽  
pp. H122-H132
Author(s):  
J. M. Jaeger ◽  
W. R. Gibbons
Keyword(s):  
Action Potential ◽  
Outward Current ◽  
Purkinje Fiber ◽  
Slow Inward Current ◽  
Channel Blockers ◽  
Inward Current ◽  
Purkinje Fibers ◽  
Cardiac Purkinje Fibers ◽  
Current Voltage ◽  
Current Voltage Relation

We have tried to answer two fundamental questions concerning the outward current IX1 of cardiac Purkinje fibers. 1) Is it possible that current changes identified as arising from IX1 in voltage-clamp experiments are actually manifestations of changes in the slow inward current (Isi); and 2) is IX1 in fact required to produce the electrical phenomena attributed to it? Isi behavior and the role of IX1 were explored using computer simulation. The Isi model produced current changes during depolarizations and hyperpolarizations from depolarized resting potentials like those attributed to IX1. It also produced a component of "tail currents" that behaved like IX1. If these current changes were analyzed, assuming that an outward current is responsible, the resulting kinetics and current voltage relation would be very similar to the kinetics and current voltage relation reported for IX1. Using the McAllister, Noble, and Tsien formulation of the Purkinje fiber action potential, we found that IX1 is not essential for repolarization of the reconstructed action potential nor is it needed to reproduce interval duration effects and the effects of applied current in that model. Data suggesting that calcium channel blockers reduce IX1 and that catecholamines increase IX1 may be explained as arising from changes in Isi. Thus many manifestations of IX1 can be explained as arising from unanticipated behavior of Isi, and IX1 does not necessarily play a key role in generating Purkinje fiber electrical activity.

scholarly journals Calcium currents in a fast-twitch skeletal muscle of the rat.

1983 ◽  
Vol 82 (4) ◽  
pp. 449-468 ◽  
Author(s):  
P L Donaldson ◽  
K G Beam
Keyword(s):  
Skeletal Muscle ◽  
Leakage Current ◽  
Calcium Current ◽  
Outward Current ◽  
Extracellular Calcium ◽  
Calcium Currents ◽  
Slow Inward Current ◽  
Delayed Rectifier ◽  
Inward Current ◽  
Time To Peak

Slow ionic currents were measured in the rat omohyoid muscle with the three-microelectrode voltage-clamp technique. Sodium and delayed rectifier potassium currents were blocked pharmacologically. Under these conditions, depolarizing test pulses elicited an early outward current, followed by a transient slow inward current, followed in turn by a late outward current. The early outward current appeared to be a residual delayed rectifier current. The slow inward current was identified as a calcium current on the basis that (a) its magnitude depended on extracellular calcium concentration, (b) it was blocked by the addition of the divalent cations cadmium or nickel, and reduced in magnitude by the addition of manganese or cobalt, and (c) barium was able to replace calcium as an inward current carrier. The threshold potential for inward calcium current was around -20 mV in 10mM extracellular calcium and about -35 mV in 2 mM calcium. Currents were net inward over part of their time course for potentials up to at least +30 mV. At temperatures of 20-26 degrees C, the peak inward current (at approximately 0 mV) was 139 +/- 14 microA/cm2 (mean +/- SD), increasing to 226 +/- 28 microA/cm2 at temperatures of 27-37 degrees C. The late outward current exhibited considerable fiber-to-fiber variability. In some fibers it was primarily a time-independent, nonlinear leakage current. In other fibers it was primarily a time-independent, nonlinear leakage current. In other fibers it appeared to be the sum of both leak and a slowly activated outward current. The rate of activation of inward calcium current was strongly temperature dependent. For example, in a representative fiber, the time-to-peak inward current for a +10-mV test pulse decreased from approximately 250 ms at 20 degrees C to 100 ms at 30 degrees C. At 37 degrees C, the time-to-peak current was typically approximately 25 ms. The earliest phase of activation was difficult to quantify because the ionic current was partially obscured by nonlinear charge movement. Nonetheless, at physiological temperatures, the rate of calcium channel activation in rat skeletal muscle is about five times faster than activation of calcium channels in frog muscle. This pathway may be an important source of calcium entry in mammalian muscle.

scholarly journals Membrane Currents in Mammalian Ventricular Heart Muscle Fibers Using a Voltage-Clamp Technique

1971 ◽  
Vol 57 (3) ◽  
pp. 290-296 ◽  
Author(s):  
Gerhard Giebisch ◽  
Silvio Weidmann
Keyword(s):  
Action Potential ◽  
Outward Current ◽  
Time Dependent ◽  
Resting Potential ◽  
Equilibrium Potential ◽  
Initial Amplitude ◽  
Inward Current ◽  
Gap Technique ◽  
Sucrose Gap

Bundles of sheep ventricular fibers were voltage-clamped utilizing a modified sucrose gap technique and intracellular voltage control. An action potential was fired off in the usual way, and the clamp circuit was switched on at preselected times during activity. Clamping the membrane back to its resting potential during the early part of an action potential resulted in a surge of inward current. The initial amplitude of this current surge decreased as the clamp was switched on progressively later during the action potential. Inward current decreasing as a function of time was also recorded if the membrane potential was clamped beyond the presumed K equilibrium potential (to -130 mv). Clamping the membrane to the inside positive range (+40 mv to +60 mv) at different times of an action potential resulted in a step of outward current which was not time-dependent. The results suggest that normal repolarization of sheep ventricle depends on a time-dependent decrease of inward current (Na, Ca) rather than on a time-dependent increase of outward current (K).

Inositol trisphosphate and activators of protein kinase C modulate membrane currents in tail motor neurons of Aplysia

1989 ◽  
Vol 61 (2) ◽  
pp. 302-310 ◽  
Author(s):  
M. Sawada ◽  
L. J. Cleary ◽  
J. H. Byrne
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Motor Neurons ◽  
Outward Current ◽  
Membrane Currents ◽  
Slow Inward Current ◽  
Apparent Increase ◽  
Inward Current ◽  
Kinase C ◽  
Hydrolysis Of

1. We have investigated how activation of the inositol lipid second messenger pathway may contribute to modulation of membrane currents in tail motor neurons of Aplysia. Specifically, we examined the effects of injected inositol 1,4,5-trisphosphate (IP3) and analogues of diacylglycerol (DAG), both of which are products of the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2). 2. Injection of IP3 produced an outward current associated with an apparent increase in membrane conductance. Ion substitution experiments, the sensitivity of the response to low concentrations of TEA and its attenuation by intracellular injections of EGTA suggest that the current produced by injection of IP3 is a calcium-activated K+ current (IK,Ca). 3. The response to IP3 was mimicked by intracellular injection of Ca2+. Injection of Ca2+ produced an outward current that was associated with an apparent increase in input conductance of the membrane. The same manipulations that affected the response to IP3 (see above) also affected the response to injections of Ca2+. 4. Injections of activators of protein kinase C (PKC) produced a relatively slow inward current. The inward current has not been fully analyzed, but it does not appear to be due to the actions of any single conventional ion channel. 5. Activators of PKC attenuated responses to subsequent injections of IP3 indicating that one component of PIP2 hydrolysis can attenuate the other. 6. The results suggest that hydrolysis of inositol phospholipids is a mechanism for regulation of membrane properties in tail motor neurons of Aplysia.

Two electrophysiologically distinct types of cultured pacemaker cells from rabbit sinoatrial node

1986 ◽  
Vol 250 (2) ◽  
pp. H325-H329 ◽  
Author(s):  
R. D. Nathan
Keyword(s):  
Sinoatrial Node ◽  
Sodium Current ◽  
Outward Current ◽  
Slow Inward Current ◽  
Transient Outward Current ◽  
Type I ◽  
Pacemaker Cells ◽  
Inward Current ◽  
Fast Transient

Previous investigations employing multicellular nodal preparations (i.e., mixtures of dominant and subsidiary pacemaker cells) have suggested that the fast transient inward sodium current (iNa) either is not present in dominant pacemaker cells or is present but inactivated at the depolarized take-off potentials that these cells exhibit. In the present study, this question was resolved by voltage clamp analysis of single pacemaker cells isolated from the sinoatrial node and maintained in vitro for 1-3 days. Two types of cells, each with a different morphology, exhibited two modes of electrophysiological behavior. Type I cells (presumably dominant pacemakers) displayed only a tetrodotoxin (TTX)-resistant (but cadmium-sensitive) slow inward current, whereas type II cells (presumably subsidiary pacemakers) exhibited two components of inward current, a TTX-sensitive, fast transient inward current and a TTX-resistant (but cadmium-sensitive) slow inward current. Three other voltage-gated currents, 1) a slowly developing inward current activated by hyperpolarization (if, ih, delta ip), 2) a transient outward current activated by strong depolarization (ito, iA), and 3) a delayed outward current, were recorded in both types of pacemaker cells.

Role of Na-Ca exchange in the action potential changes caused by drive in cardiac myocytes exposed to different Ca2+ loads

1999 ◽  
Vol 77 (6) ◽  
pp. 383-397
Author(s):  
Qi-Ying Liu ◽  
Mario Vassalle
Keyword(s):  
Action Potentials ◽  
Ventricular Myocytes ◽  
Outward Current ◽  
Time Dependent ◽  
Inward Current ◽  
Tail Current ◽  
Outward Currents ◽  
Inward Currents ◽  
Single Ventricular Myocytes

The role of Na-Ca exchange in the membrane potential changes caused by repetitive activity ("drive") was studied in guinea pig single ventricular myocytes exposed to different [Ca2+]o. The following results were obtained. (i) In 5.4 mM [Ca2+]o, the action potentials (APs) gradually shortened during drive, and the outward current during a train of depolarizing voltage clamp steps gradually increased. (ii) The APs shortened more and were followed by a decaying voltage tail during drive in the presence of 5 mM caffeine; the outward current became larger and there was an inward tail current on repolarization during a train of depolarizing steps. (iii) These effects outlasted drive so that immediately after a train of APs, currents were already bigger and, after a train of steps, APs were already shorter. (iv) In 0.54 mM [Ca2+]o, the above effects were much smaller. (v) In high [Ca2+]o APs were shorter and outward currents larger than in low [Ca2+]o. (vi) In 10.8 mM [Ca2+]o, both outward and inward currents during long steps were exaggerated by prior drive, even with steps (+80 and +120 mV) at which there was no apparent inward current identifiable as ICa. (vii) In 0.54 mM [Ca2+]o, the time-dependent outward current was small and prior drive slightly increased it. (viii) During long steps, caffeine markedly increased outward and inward tail currents, and these effects were greatly decreased by low [Ca2+]o. (ix) After drive in the presence of caffeine, Ni2+ decreased the outward and inward tail currents. It is concluded that in the presence of high [Ca2+]o drive activates outward and inward Na-Ca exchange currents. During drive, the outward current participates in the plateau shortening and the inward tail current in the voltage tail after the action potential.Key words: ventricular myocytes, repetitive activity, outward and inward Na-Ca exchange currents, caffeine, nickel.

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