Existence of a transient outward K+ current in guinea pig cardiac myocytes

2000 ◽  
Vol 279 (1) ◽  
pp. H130-H138 ◽  
Author(s):  
Gui-Rong Li ◽  
Baofeng Yang ◽  
Haiying Sun ◽  
Clive M. Baumgarten
Keyword(s):  
Guinea Pig ◽  
Ventricular Myocytes ◽  
Outward Current ◽  
Resting Potential ◽  
Transient Outward Current ◽  
Time Constants ◽  
Zero Current ◽  
Steady State Inactivation ◽  
K Current ◽  
External K

A novel transient outward K+current that exhibits inward-going rectification ( I to.ir) was identified in guinea pig atrial and ventricular myocytes. I to.ir was insensitive to 4-aminopyridine (4-AP) but was blocked by 200 μmol/l Ba2+or removal of external K+. The zero current potential shifted 51–53 mV/decade change in external K+. I to.ir density was twofold greater in ventricular than in atrial myocytes, and biexponential inactivation occurs in both types of myocytes. At −20 mV, the fast inactivation time constants were 7.7 ± 1.8 and 6.1 ± 1.2 ms and the slow inactivation time constants were 85.1 ± 14.8 and 77.3 ± 10.4 ms in ventricular and atrial cells, respectively. The midpoints for steady-state inactivation were −36.4 ± 0.3 and −51.6 ± 0.4 mV, and recovery from inactivation was rapid near the resting potential (time constants = 7.9 ± 1.9 and 8.8 ± 2.1 ms, respectively). I to.ir was detected in Na+-containing and Na+-free solutions and was not blocked by 20 nmol/l saxitoxin. Action potential clamp revealed that I to.ir contributed an outward current that activated rapidly on depolarization and inactivated by early phase 2 in both tissues. Although it is well known that 4-AP-sensitive transient outward current is absent in guinea pig, this Ba2+-sensitive and 4-AP-insensitive K+ current has been overlooked.

Transient outward current carried by inwardly rectifying K+ channels in guinea pig ventricular myocytes dialyzed with low-K+ solution

2004 ◽  
Vol 287 (5) ◽  
pp. C1396-C1403 ◽  
Author(s):  
Pavel Zhabyeyev ◽  
Tatsuya Asai ◽  
Sergey Missan ◽  
Terence F. McDonald
Keyword(s):  
Guinea Pig ◽  
Ventricular Myocytes ◽  
Outward Current ◽  
Transient Outward Current ◽  
K Channels ◽  
Voltage Gated ◽  
Voltage Gated Channels ◽  
Inwardly Rectifying ◽  
Low K ◽  
External K

There have been periodic reports of nonclassic (4-aminopyridine insensitive) transient outward K+ current in guinea pig ventricular myocytes, with the most recent one describing a novel voltage-gated inwardly rectifying type. In the present study, we have investigated a transient outward current that overlaps inward Ca2+ current ( ICa,L) in myocytes dialyzed with 10 mM K+ solution and superfused with Tyrode’s solution. Although depolarizations from holding potential ( Vhp) −40 to 0 mV elicited relatively small inward ICa,L in these myocytes, removal of external K+ or addition of 0.2 mM Ba2+ more than doubled the amplitude of the current. The basis of the enhancement of ICa,L was the suppression of a large transient outward K+ current. Similar enhancement was observed when Vhp was moved to −80 mV and test depolarizations were preceded by short prepulses to −40 mV. Investigation of the time and voltage properties of the outward K+ transient indicated that it was inwardly rectifying and unlikely to be carried by voltage-gated channels. The outward transient was attenuated in myocytes dialyzed with high-Mg2+ solution, accelerated in myocytes dialyzed with 100 μM spermine solution, and abolished with time in myocytes dialyzed with ATP-free solution. These and other findings suggest that the outward transient is a component of classic “time-independent” inwardly rectifying K+ current.

Electrophysiological and functional effects of adenosine on ventricular myocytes of various mammalian species

1996 ◽  
Vol 271 (4) ◽  
pp. C1233-C1243 ◽  
Author(s):  
Y. Song ◽  
L. Belardinelli
Keyword(s):  
Guinea Pig ◽  
Action Potential ◽  
Ventricular Myocytes ◽  
Mammalian Species ◽  
Outward Current ◽  
Binding Studies ◽  
Outward Currents ◽  
K Current ◽  
Rabbit Ventricular Myocytes ◽  
A1 Adenosine Receptors

The goal of this study was to determine the electrophysiological and functional effects of adenosine on ventricular myocytes of guinea pig, rabbit, rat, and ferret hearts. Adenosine (100 microM) shortened the action potential durations of rat and ferret myocytes by 14 +/- 1 and 57 +/- 7%, reduced the amplitudes of cell twitch shortening by 13 +/- 1 and 54 +/- 5%, and increased outward currents by 15 +/- 4 and 55 +/- 5%, respectively, but had no effect on guinea pig and rabbit myocytes. The properties of adenosine-activated outward current in rat and ferret ventricular myocytes indicated that this current is the adenosine-sensitive K+ current [IK(Ado)]. Adenosine had no significant effect on basal Ca2+ current but specifically inhibited isoproterenol-stimulated L-type Ca2+ current in myocytes of all species studied. Binding studies revealed that the density of A1 adenosine receptors (A1AdoR) was highest in ferret and lowest in rabbit myocytes, but the differential effects of adenosine among species could not be solely explained by differences in A1AdoR density. In summary, adenosine shortened the action potential and reduced the twitch shortening of rat and ferret but not of guinea pig and rabbit ventricular myocytes. Shortening of the action potential was associated with the activation of IK(Ado). The anti-beta-adrenergic action of adenosine appeared to be independent of species.

scholarly journals Ca2+ Overload Evokes a Transient Outward Current in Guinea-Pig Ventricular Myocytes

2002 ◽  
Vol 66 (1) ◽  
pp. 87-92 ◽  
Author(s):  
Ichirota Nakajima ◽  
Hiroyuki Watanabe ◽  
Kenji Iino ◽  
Takashi Saito ◽  
Mamoru Miura
Keyword(s):  
Guinea Pig ◽  
Ventricular Myocytes ◽  
Outward Current ◽  
Transient Outward Current

scholarly journals The calcium-independent transient outward potassium current in isolated ferret right ventricular myocytes. II. Closed state reverse use-dependent block by 4-aminopyridine.

1993 ◽  
Vol 101 (4) ◽  
pp. 603-626 ◽  
Author(s):  
D L Campbell ◽  
Y Qu ◽  
R L Rasmusson ◽  
H C Strauss
Keyword(s):  
Steady State ◽  
Right Ventricular ◽  
Ventricular Myocytes ◽  
Patch Clamp Technique ◽  
Time Constants ◽  
Closed State ◽  
Whole Cell Patch Clamp ◽  
Dependent Behavior ◽  
Steady State Inactivation ◽  
K Current

Block of the calcium-independent transient outward K+ current, I(to), by 4-aminopyridine (4-AP) was studied in ferret right ventricular myocytes using the whole cell patch clamp technique. 4-AP reduces I(to) through a closed state blocking mechanism displaying "reverse use-dependent" behavior that was inferred from: (a) development of tonic block at hyperpolarized potentials; (b) inhibition of development of tonic block at depolarized potentials; (c) appearance of "crossover phenomena" in which the peak current is delayed in the presence of 4-AP at depolarized potentials; (d) relief of block at depolarized potentials which is concentration dependent and parallels steady-state inactivation for low 4-AP concentrations (V1/2 approximately -10 mV in 0.1 mM 4-AP) and steady-state activation at higher concentrations (V1/2 = +7 mV in 1 mM 4-AP, +15 mV in 10 mM 4-AP); and (e) reassociation of 4-AP at hyperpolarized potentials. No evidence for interaction of 4-AP with either the open or inactivated state of the I(to) channel was obtained from measurements of kinetics of recovery and deactivation in the presence of 0.5-1.0 mM 4-AP. At hyperpolarized potentials (-30 to -90 mV) 10 mM 4-AP associates slowly (time constants ranging from approximately 800 to 1,300 ms) with the closed states of the channel (apparent Kd approximately 0.2 mM). From -90 to -20 mV the affinity of the I(to) channel for 4-AP appears to be voltage insensitive; however, at depolarized potentials (+20 to +100 mV) 4-AP dissociates with time constants ranging from approximately 350 to 150 ms. Consequently, the properties of 4-AP binding to the I(to) channel undergo a transition in the range of potentials over which channel activation and inactivation occurs (-30 to +20 mV). We propose a closed state model of I(to) channel gating and 4-AP binding kinetics, in which 4-AP binds to three closed states. In this model 4-AP has a progressively lower affinity as the channel approaches the open state, but has no intrinsic voltage dependence of binding.

scholarly journals The calcium-independent transient outward potassium current in isolated ferret right ventricular myocytes. I. Basic characterization and kinetic analysis.

1993 ◽  
Vol 101 (4) ◽  
pp. 571-601 ◽  
Author(s):  
D L Campbell ◽  
R L Rasmusson ◽  
Y Qu ◽  
H C Strauss
Keyword(s):  
Steady State ◽  
Ventricular Myocytes ◽  
Nonlinear Least Squares ◽  
Patch Clamp Technique ◽  
Time Constants ◽  
Whole Cell Patch Clamp ◽  
Voltage Dependent ◽  
Steady State Inactivation ◽  
K Current ◽  
Necessary And Sufficient

Enzymatically isolated myocytes from ferret right ventricles (12-16 wk, male) were studied using the whole cell patch clamp technique. The macroscopic properties of a transient outward K+ current I(to) were quantified. I(to) is selective for K+, with a PNa/PK of 0.082. Activation of I(to) is a voltage-dependent process, with both activation and inactivation being independent of Na+ or Ca2+ influx. Steady-state inactivation is well described by a single Boltzmann relationship (V1/2 = -13.5 mV; k = 5.6 mV). Substantial inactivation can occur during a subthreshold depolarization without any measurable macroscopic current. Both development of and recovery from inactivation are well described by single exponential processes. Ensemble averages of single I(to) channel currents recorded in cell-attached patches reproduce macroscopic I(to) and indicate that inactivation is complete at depolarized potentials. The overall inactivation/recovery time constant curve has a bell-shaped potential dependence that peaks between -10 and -20 mV, with time constants (22 degrees C) ranging from 23 ms (-90 mV) to 304 ms (-10 mV). Steady-state activation displays a sigmoidal dependence on membrane potential, with a net aggregate half-activation potential of +22.5 mV. Activation kinetics (0 to +70 mV, 22 degrees C) are rapid, with I(to) peaking in approximately 5-15 ms at +50 mV. Experiments conducted at reduced temperatures (12 degrees C) demonstrate that activation occurs with a time delay. A nonlinear least-squares analysis indicates that three closed kinetic states are necessary and sufficient to model activation. Derived time constants of activation (22 degrees C) ranged from 10 ms (+10 mV) to 2 ms (+70 mV). Within the framework of Hodgkin-Huxley formalism, Ito gating can be described using an a3i formulation.

Tedisamil inactivates transient outward K+ current in rat ventricular myocytes

1989 ◽  
Vol 257 (5) ◽  
pp. H1746-H1749 ◽  
Author(s):  
I. D. Dukes ◽  
M. Morad
Keyword(s):  
Ventricular Myocytes ◽  
Sodium Current ◽  
Outward Current ◽  
Cell Voltage ◽  
Transient Outward Current ◽  
Dependent Manner ◽  
Rat Ventricular Myocytes ◽  
K Current ◽  
New Type ◽  
Inwardly Rectifying

The action of tedisamil, a new bradycardiac agent with antiarrhythmic properties, was investigated in single rat ventricular myocytes using the whole cell voltage-clamp technique. Under current clamp conditions, 1-20 microM tedisamil caused marked prolongations of the action potential. Over the same concentration range, in voltage-clamped myocytes, tedisamil suppressed the transient outward current (ito) and enhanced its inactivation in a dose-dependent manner. The half-maximal dose for the effect of tedisamil on ito was approximately 6 microM. Tedisamil had no significant effects on the inwardly rectifying potassium current and calcium current but did suppress the sodium current at concentrations greater than 20 microM. Our findings suggest that tedisamil represents a new type of antiarrhythmic agent that primarily suppresses the transient outward K+ current.

Is there an A-type K+ current in guinea pig ventricular myocytes?

2003 ◽  
Vol 284 (2) ◽  
pp. H598-H604 ◽  
Author(s):  
Ian Findlay
Keyword(s):  
Guinea Pig ◽  
Voltage Dependence ◽  
Ventricular Myocytes ◽  
Reversal Potential ◽  
Outward Current ◽  
Type K ◽  
K Current

A unique transient outward K+ current ( I to) has been described to result from the removal of extracellular Ca2+ from ventricular myocytes of the guinea pig (15). This study addressed the question of whether this current represented K+-selective I to or the efflux of K+ via L-type Ca2+ channels. This outward current was inhibited by Cd2+, Ni2+, Co2+, and La3+ as well as by nifedipine. All of these compounds were equally effective inhibitors of the L-type Ca2+ current. The current was not inhibited by 4-aminopyridine. Apparent inhibition of the outward current by extracellular Ca2+ was shown to result from the displacement of the reversal potential of cation flux through L-type Ca2+ channels. The current was found not to be K+ selective but also permeant to Cs+. The voltage dependence of inactivation of the outward current was identical to that of the L-type Ca2+ current. It is concluded that extracellular Ca2+ does not mask an A-type K+current in guinea pig ventricular myocytes.

Involvement of anion channel(s) in the modulation of the transient outward K+ channel in rat ventricular myocytes

2004 ◽  
Vol 287 (1) ◽  
pp. C163-C170 ◽  
Author(s):  
Xiao-Gang Lai ◽  
Jun Yang ◽  
Shi-Sheng Zhou ◽  
Jun Zhu ◽  
Gui-Rong Li ◽  
...  
Keyword(s):  
Steady State ◽  
Ventricular Myocytes ◽  
Ionic Current ◽  
Outward Current ◽  
Anion Channel ◽  
K Channel ◽  
Transient Outward Current ◽  
Inactivation Curve ◽  
Phalloidin Staining ◽  
Steady State Inactivation

The cardiac Ca2+-independent transient outward K+ current ( Ito), a major repolarizing ionic current, is markedly affected by Cl− substitution and anion channel blockers. We reexplored the mechanism of the action of anions on Ito by using whole cell patch-clamp in single isolated rat cardiac ventricular myocytes. The transient outward current was sensitive to blockade by 4-aminopyridine (4-AP) and was abolished by Cs+ substitution for intracellular K+. Replacement of most of the extracellular Cl− with less permeant anions, aspartate (Asp−) and glutamate (Glu−), markedly suppressed the current. Removal of external Na+ or stabilization of F-actin with phalloidin did not significantly affect the inhibitory action of less permeant anions on Ito. In contrast, the permeant Cl− substitute Br− did not markedly affect the current, whereas F− substitution for Cl− induced a slight inhibition. The Ito elicited during Br− substitution for Cl− was also sensitive to blockade by 4-AP. The ability of Cl− substitutes to induce rightward shifts of the steady-state inactivation curve of Ito was in the following sequence: NO3− > Cl− ≈ Br− > gluconate− > Glu− > Asp−. Depolymerization of actin filaments with cytochalasin D (CytD) induced an effect on the steady-state inactivation of Ito similar to that of less permeant anions. Fluorescent phalloidin staining experiments revealed that CytD-pretreatment significantly decreased the intensity of FITC-phalloidin staining of F-actin, whereas Asp− substitution for Cl− was without significant effect on the intensity. These results suggest that the Ito channel is modulated by anion channel(s), in which the actin cytoskeleton may be implicated.

Decreased transient outward K+ current in ventricular myocytes from acromegalic rats

1991 ◽  
Vol 260 (3) ◽  
pp. H935-H942 ◽  
Author(s):  
X. P. Xu ◽  
P. M. Best
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Time Course ◽  
Ventricular Myocytes ◽  
Outward Current ◽  
Resting Potential ◽  
Gh3 Cells ◽  
Heart Weight ◽  
Transient Outward Current ◽  
Tumor Bearing

Cardiac hypertrophy and heart failure are common to acromegalic patients who have abnormally high serum growth hormone (GH). While the function of cardiac muscle is clearly affected by chronically elevated GH, the electrical activity of myocytes from hearts with GH-dependent hypertrophy has not been studied. We used adult, female Wistar-Furth rats with induced GH-secreting tumors to study the effect of excessive GH on ion channels of cardiac myocytes. GH-secreting tumors were induced by subcutaneous inoculation of GH3 cells. Eight weeks after inoculation, the rats had doubled their body weight and heart size compared with age-matched controls. There were no differences in either action potential amplitude or resting potential of right ventricular myocytes from control and tumor-bearing rats. However, action potential duration increased significantly in tumor-bearing rats; the time to 50% repolarization was 23 +/- 14 ms (n = 10) compared with 6.6 +/- 1.5 ms (n = 14) in controls. The prolongation of the action potential was mainly due to a decrease in density of a transient outward current (It,o) carried by K+. The normalized conductance for It,o decreased from 0.53 +/- 0.10 nS/pF (n = 25) in controls to 0.33 +/- 0.09 nS/pF (n = 26) in tumor-bearing rats. The decrease in It,o) and increase in heart weight occurred with a similar time course. The increased action potential duration prolongs Ca2+ influx through L-type Ca2+ channels in the tumor-bearing animals; this may be important in cardiovascular adaptation.

Roles of Ca2+ and Na+ in the inward current and action potentials of guinea pig ureteral myocytes

1997 ◽  
Vol 272 (2) ◽  
pp. C535-C542 ◽  
Author(s):  
J. L. Sui ◽  
C. Y. Kao
Keyword(s):  
Guinea Pig ◽  
Action Potentials ◽  
Outward Current ◽  
Membrane Conductance ◽  
Membrane Current ◽  
Resting Potential ◽  
Inward Current ◽  
K Current ◽  
Free Media ◽  
Ca2 Channels

Physiological roles of Ca2+ vs. Na+ in membrane currents and action potentials of ureteral myocytes were investigated on freshly dissociated guinea pig ureteral myocytes with the patch-clamp method. The myocytes are spindle shaped, with cell volume of 2,473 microm3, surface area of 2,014 microm2, capacitance of 48.2 pF, resting potential of -47.9 mV, and membrane conductance of 840 pS. The membrane current consists of a slow inward Ca2+ current (ICa) conducted by L-type Ca2+ channels and an actively fluctuating Ca2+-activated K+ current [IK(Ca)] conducted by Ca2+-activated maxi-K+ channels. ICa dominates the membrane current by being long lasting and more active at less depolarized potentials than IK(Ca) and by regulating IK(Ca). Ca2+-free media, Co2+, and nifedipine reduce or block ICa, whereas high extracellular Ca2+ concentration and BAY K 8644 enhance it. Action potential amplitudes and plateaus are regulated correspondingly. Related changes are also seen in IK(Ca) In contrast, no fast inward current attributable to Na+ was found. Replacing extracellular Na+ with tris(hydroxymethyl)aminomethane had no apparent effects on the inward or outward current or on the action potentials.

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