Delayed rectifier K+ current in rabbit atrial myocytes

1995 ◽  
Vol 269 (2) ◽  
pp. H524-H532 ◽  
Author(s):  
K. Muraki ◽  
Y. Imaizumi ◽  
M. Watanabe ◽  
Y. Habuchi ◽  
W. R. Giles
Keyword(s):  
Maximum Amplitude ◽  
Outward Current ◽  
Cell Voltage ◽  
Inward Rectification ◽  
Resting Membrane Potential ◽  
Delayed Rectifier ◽  
Wave Form ◽  
Class Iii ◽  
Atrial Myocytes ◽  
K Current

The role of delayed rectifier K+ current(s) (IK) in rabbit left atrium was examined by applying the whole cell voltage-clamp technique to isolated single myocytes. Right-triangular waveforms, which mimic the shape of atrial action potentials (APs), and selective blockers were used to compare the contribution of IK with other K+ currents to repolarization of the APs. IK measured at 34 degrees C in atrial myocytes was very small; the maximum peak amplitude of the tail current (IK,tail) at -40 mV was approximately 50 pA. The IK,tail was almost abolished in most cells (approximately 80%) by the application of 1 microM E-4031, a class III antiarrhythmic drug. The E-4031-sensitive current recorded with the triangular command wave-form showed strong inward rectification and had a maximum amplitude of approximately 30 pA at -40 mV. Total outward current elicited by triangular command pulses depended strongly on stimulation frequency. The main frequency-dependent component was a Ca(2+)-independent transient K+ current (I(t)). I(t) elicited by triangular pulses at 1 Hz was substantially reduced by 4-aminopyridine (4-AP) at potentials positive to 0 mV but was not changed significantly by 1 microM E-4031; 100 microM E-4031 reduced I(t) by approximately 30%. The shape of the APs which were recorded from a single rabbit atrial cell strongly depended on the pulse frequency. Application of 1 microM E-4031 increased action potential duration (APD) in > 50% of cells examined but had little effect on the resting membrane potential (RMP). Application of 0.1 mM BaCl2 also lengthened APD and reduced RMP by approximately 20 mV.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Two components of cardiac delayed rectifier K+ current. Differential sensitivity to block by class III antiarrhythmic agents.

1990 ◽  
Vol 96 (1) ◽  
pp. 195-215 ◽  
Author(s):  
M C Sanguinetti ◽  
N K Jurkiewicz
Keyword(s):  
Antiarrhythmic Agent ◽  
Reversal Potential ◽  
Differential Sensitivity ◽  
Inward Rectification ◽  
Delayed Rectifier ◽  
Antiarrhythmic Agents ◽  
Class Iii ◽  
Activation Curve ◽  
Voltage Range ◽  
K Current

An envelope of tails test was used to show that the delayed rectifier K+ current (IK) of guinea pig ventricular myocytes results from the activation of two outward K+ currents. One current was specifically blocked by the benzenesulfonamide antiarrhythmic agent, E-4031 (IC50 = 397 nM). The drug-sensitive current, "IKr" exhibits prominent rectification and activates very rapidly relative to the slowly activating drug-insensitive current, "IKs." IKs was characterized by a delayed onset of activation that occurs over a voltage range typical of the classically described cardiac IK. Fully activated IKs, measured as tail current after 7.5-s test pulses, was 11.4 times larger than the fully activated IKr. IKr was also blocked by d-sotalol (100 microM), a less potent benzenesulfonamide Class III antiarrhythmic agent. The activation curve of IKr had a steep slope (+7.5 mV) and a negative half-point (-21.5 mV) relative to the activation curve of IKs (slope = +12.7 mV, half-point = +15.7 mV). The reversal potential (Erev) of IKr (-93 mV) was similar to EK (-94 mV for [K+]o = 4 mM), whereas Erev of IKs was -77 mV. The time constants for activation and deactivation of IKr made up a bell-shaped function of membrane potential, peaking between -30 and -40 mV (170 ms). The slope conductance of the linear portion of the fully activated IKr-V relation was 22.5 S/F. Inward rectification of this relation occurred at potentials greater than -50 mV, resulting in a voltage-dependent decrease in peak IKr at test potentials greater than 0 mV. Peak IKr at 0 mV averaged 0.8 pA/pF (n = 21). Although the magnitude of IKr was small relative to fully activated IKs, the two currents were of similar magnitude when measured during a relatively short pulse protocol (225 ms) at membrane potentials (-20 to +20 mV) typical of the plateau phase of cardiac action potentials.

Membrane depolarization in PC-12 cells during hypoxia is regulated by an O2-sensitive K+ current

1996 ◽  
Vol 271 (2) ◽  
pp. C658-C665 ◽  
Author(s):  
W. H. Zhu ◽  
L. Conforti ◽  
M. F. Czyzyk-Krzeska ◽  
D. E. Millhorn
Keyword(s):  
Membrane Potential ◽  
Reversal Potential ◽  
Outward Current ◽  
Cell Voltage ◽  
Membrane Depolarization ◽  
Resting Membrane Potential ◽  
Current Clamp ◽  
Pc 12 Cells ◽  
Current Voltage ◽  
K Current

The effects of hypoxia on K+ current (IK), resting membrane potential, and cytosolic free Ca2+ in rat pheochromocytoma (PC-12) cells were studied. Whole cell voltage- and current-clamp experiments were performed to measure IK and membrane potential, respectively. Cytosolic free Ca2+ level was measured using the Ca(2+)-sensitive fluorescent dye fura 2. Depolarizing voltage steps to +50 mV from a holding potential of -90 mV elicited a slowly inactivating, tetraethylammonium chloride-sensitive, and Ca(2+)-insensitive IK that was reversibly inhibited by reduced O2 tension. Graded reduction in PO2 (from 150 to 0 mmHg) induced a graded inhibition of O2-sensitive IK [IK(O2)] up to 46% at 0 mmHg. Moreover, hypoxia induced a 19-mV membrane depolarization and a twofold increase in cytosolic free Ca2+. In Ca(2+)-free condition, inhibition of IK(O2) induced an 8-mV depolarization, suggesting that inhibition of IK(O2) was responsible for initiating depolarization. The effect of reduced PO2 on the current-voltage relationship showed a reduction of outward current and a 14-mV shift in the reversal potential comparable with the amount of depolarization measured in current clamp experiments. Neither Ca(2+)-activated IK nor inwardly rectifying IK are responsible for the hypoxia-induced depolarization. In conclusion, PC-12 cells express an IK(O2), inhibition of which leads to membrane depolarization and increased intracellular Ca2+, making the PC-12 clonal cell line a useful model for studying the molecular and biophysical mechanisms that mediate O2 chemosensitivity.

Role of chloride currents in repolarizing rabbit atrial myocytes

1995 ◽  
Vol 268 (5) ◽  
pp. H1992-H2002 ◽  
Author(s):  
Z. Wang ◽  
B. Fermini ◽  
J. Feng ◽  
S. Nattel
Keyword(s):  
Action Potential ◽  
Reversal Potential ◽  
Outward Current ◽  
Cell Voltage ◽  
Disulfonic Acid ◽  
Transient Outward Current ◽  
Atrial Myocytes ◽  
Atrial Cells ◽  
K Current

Rabbit atrial cells manifest a prominent transient outward K+ current (Ito1), but this current recovers slowly from inactivation and is unlikely to be important at physiological rates (3-5 Hz). Depolarization of rabbit atrial cells also elicits a transient Ca(2+)-dependent outward Cl- current (Ito2). To compare the relative magnitude of these transient outward currents at various rates, we applied whole cell voltage-clamp techniques to isolated rabbit atrial myocytes. Whereas peak Ito1 exceeded Ito2 at slow rates (0.1 Hz), Ito1 was strongly reduced as rate was increased (by 97 +/- 2%, mean +/- SE, at 4 Hz), while Ito2 was slightly reduced (by 28 +/- 4%, 4 Hz). The reversal potential of transient outward tail currents at 0.07 Hz was -49 +/- 9 mV, while at 2.5 Hz the reversal potential became -18 +/- 7 mV (calculated Cl- reversal potential -18 mV). The addition of the Cl- transport blocker 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS; 150 microM) or the replacement of external Cl- with methanesulfonate inhibited a large part of the transient outward current elicited by depolarization at 4 Hz. DIDS and Cl- replacement increased action potential duration in both single rabbit atrial cells and multicellular rabbit atrial preparations. We conclude that the Ca(2+)-dependent Cl- current is substantially larger than the transient K+ current at physiological rates in the rabbit and is likely to play a more important role in action potential repolarization than the latter current in this tissue in vivo.

Characterization of macroscopic outward currents of canine colonic myocytes

1989 ◽  
Vol 257 (3) ◽  
pp. C461-C469 ◽  
Author(s):  
W. C. Cole ◽  
K. M. Sanders
Keyword(s):  
Outward Current ◽  
Cell Voltage ◽  
Muscle Cells ◽  
Time Dependent ◽  
Delayed Rectifier ◽  
Delayed Rectifier Current ◽  
Outward Currents ◽  
Voltage Dependent ◽  
K Current ◽  
Time Courses

Outward currents of colonic smooth muscle cells were characterized by the whole cell voltage-clamp method. Four components of outward current were identified: a time-independent and three time-dependent components. The time-dependent current showed strong outward rectification positive to -25 mV and was blocked by tetraethylammonium. The time-dependent components were separated on the basis of their time courses, voltage dependence, and pharmacological sensitivities. They are as follows. 1) A Ca2+-activated K current sensitive to external Ca2+ and Ca2+ influx was blocked by ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (0.1 X 10(-3) M) and nifedipine (1 X 10(-6) and was increased by elevated Ca2+ (8 X 10(-6) M) and BAY K 8644 (1 X 10(-6) M). 2) A "delayed rectifier" current was observed that decayed slowly with time and showed no voltage-dependent inactivation. 3) Spontaneous transient outward currents that were blocked by ryanodine (2 X 10(-6) M) were also recorded. The possible contributions of these currents to the electrical activity of colonic muscle cells in situ are discussed. Ca2+-activated K current may contribute a significant conductance to the repolarizing phase of electrical slow waves.

scholarly journals Effects of Sematilide, a Novel Class III Antiarrhythmic Agent, on Delayed Rectifier K+ Current in Guinea Pig Atrial Myocytes

1996 ◽  
Vol 71 (4) ◽  
pp. 361-365 ◽  
Author(s):  
Yasunori Ishii ◽  
Katsuhiko Muraki ◽  
Atsushi Kurihara ◽  
Yuji Imaizumi ◽  
Minoru Watanabe
Keyword(s):  
Guinea Pig ◽  
Antiarrhythmic Agent ◽  
Delayed Rectifier ◽  
Class Iii ◽  
Atrial Myocytes ◽  
K Current ◽  
Class Iii Antiarrhythmic Agent

A rapidly activating delayed rectifier K+ current regulates pacemaker activity in adult mouse sinoatrial node cells

2004 ◽  
Vol 286 (5) ◽  
pp. H1757-H1766 ◽  
Author(s):  
Robert B. Clark ◽  
Matteo E. Mangoni ◽  
Andreas Lueger ◽  
Brigitte Couette ◽  
Joel Nargeot ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Action Potential ◽  
Adult Mouse ◽  
Sinoatrial Node ◽  
Physiological Role ◽  
Inward Rectification ◽  
Delayed Rectifier ◽  
Pacemaker Activity ◽  
Class Iii ◽  
K Current

We have investigated the physiological role of the “rapidly activating” delayed rectifier K+ current ( IKr) in pacemaker activity in isolated sinoatrial node (SAN) myocytes and the expression of mouse ether-a-go-go (mERG) genes in the adult mouse SAN. In isolated, voltage-clamped SAN cells, outward currents evoked by depolarizing steps (greater than –40 mV) were strongly inhibited by the class III methanesulfonanilide compound E-4031 (1–2.5 μM), and the deactivation “tail” currents that occurred during repolarization to a membrane potential of –45 mV were completely blocked. E-4031-sensitive currents ( IKr) reached a maximum at a membrane potential of –10 mV and showed pronounced inward rectification at more-positive membrane potentials. Activation of IKr occurred at –40 to 0 mV, with half-activation at about –24 mV. The contribution of IKr to action potential repolarization and diastolic depolarization was estimated by determining the E-4031-sensitive current evoked during voltage clamp with a simulated mouse SAN action potential. IKr reached its peak value (∼0.6 pA/pF) near –25 mV, close to the midpoint of the repolarization phase of the simulated action potential, and deactivated almost completely during the diastolic interval. E-4031 (1 μM) slowed the spontaneous pacing rate of Langendorff-perfused, isolated adult mouse hearts by an average of 36.5% ( n = 5). Expression of mRNA corresponding to three isoforms coded by the mouse ERG1 gene (mERG1), mERG1a, mERG1a′, and mERG1b, was consistently found in the SAN. Our data provide the first detailed characterization of IKr in adult mouse SAN cells, demonstrate that this current plays an important role in pacemaker activity, and indicate that multiple isoforms of mERG1 can contribute to native SAN IKr.

Choline chloride activates time-dependent and time-independent K+ currents in dog atrial myocytes

1994 ◽  
Vol 266 (1) ◽  
pp. C42-C51 ◽  
Author(s):  
B. Fermini ◽  
S. Nattel
Keyword(s):  
Choline Chloride ◽  
Outward Current ◽  
Time Dependent ◽  
Equilibrium Potential ◽  
Delayed Rectifier ◽  
Atrial Myocytes ◽  
Patch Clamp Technique ◽  
Voltage Dependent ◽  
K Current ◽  
K Currents

Using the whole cell configuration of the patch-clamp technique, we studied the effect of isotonic replacement of bath sodium chloride (NaCl) by choline chloride (ChCl) in dog atrial myocytes. Our results show that ChCl triggered 1) activation of a time-independent background current, characterized by a shift of the holding current in the outward direction at potentials positive to the K+ equilibrium potential (EK), and 2) activation of a time- and voltage-dependent outward current, following depolarizing voltage steps positive to EK. Because the choline-induced current obtained by depolarizing steps exhibited properties similar to the delayed rectifier K+ current (IK), we named it IKCh. The amplitude of IKCh was determined by extracellular ChCl concentration, and this current was generally undetectable in the absence of ChCl. IKCh was not activated by acetylcholine (0.001-1.0 mM) or carbachol (10 microM) and could not be recorded in the absence of ChCl or when external NaCl was replaced by sucrose or tetramethylammonium chloride. IKCh was inhibited by atropine (0.01-1.0 microM) but not by the M1 antagonist pirenzepine (up to 10 microM). This current was carried mainly by K+ and was inhibited by CsCl (120 mM, in the pipette) or barium (1 mM, in the bath). We conclude that in dog atrial myocytes, ChCl activates a background conductance comparable to ACh-dependent K+ current, together with a time-dependent K+ current showing properties similar to IK.

Lanthanum blocks a specific component of IK and screens membrane surface change in cardiac cells

1990 ◽  
Vol 259 (6) ◽  
pp. H1881-H1889 ◽  
Author(s):  
M. C. Sanguinetti ◽  
N. K. Jurkiewicz
Keyword(s):  
Ventricular Myocytes ◽  
Membrane Surface ◽  
Surface Membrane ◽  
Cell Voltage ◽  
Cardiac Cells ◽  
Delayed Rectifier ◽  
Class Iii ◽  
Surface Charges ◽  
K Current ◽  
Unidentified Component

Delayed rectifier outward K+ current (IK) in guinea pig ventricular myocytes represents the sum of two currents: a slowly activating delayed rectifier K+ current (IK.s) and a relatively rapidly activating delayed rectifier K+ current (IK.r), which rectifies at positive potentials and is specifically blocked by the class III antiarrhythmic agent, E-4031. La3+ was previously reported to block an unidentified component of IK in these cells. We used the whole cell voltage-clamp technique on isolated myocytes and confirmed these results: we show that the current blocked by La3+ (greater than or equal to 1 microM) is IK.r. This block is not caused by La3+ displacement of surface-bound Ca2+. Thus, in the presence of either E-4031 or La3+, IK represents the activation of a single current, IK.s. La3+ (10 microM-1 mM) also caused a positive shift in the voltage dependence of the activation curve of IK.s. When we assumed that La3+ acts to bind and screen negative surface charges on the outer sarcolemmal membrane, the external surface potential of these cells (in 1.8 mM Ca2+) could be estimated to be -19 mV. A modification of the Gouy-Chapman equation was used to estimate the equilibrium constant for La3+ binding (10.7 mM-1) and the minimum spacing between the negative charges on the surface membrane (22 A).

Delayed rectifier outward K+ current is composed of two currents in guinea pig atrial cells

1991 ◽  
Vol 260 (2) ◽  
pp. H393-H399 ◽  
Author(s):  
M. C. Sanguinetti ◽  
N. K. Jurkiewicz
Keyword(s):  
Guinea Pig ◽  
Inward Rectification ◽  
Delayed Rectifier ◽  
Class Iii ◽  
Activation Curve ◽  
Atrial Cells ◽  
Ventricular Cells ◽  
Steady State Current ◽  
Slope Factor ◽  
K Current

The delayed rectifier outward K+ current (IK) was studied in isolated guinea pig atrial myocytes using the whole cell voltage-clamp technique. Similar to previous findings in ventricular cells, IK of atrial cells is the composite of two distinct components: IK,r, a rapidly activating current that exhibits strong inward rectification and IK,s, a slowly activating current with only modest rectification. IK,r was defined by its sensitivity to block by Co2+ and the class III antiarrhythmic agent, E-4031. IK,r underlies the prominent outward "hump" (between -30 and +40 mV) in the steady-state current-voltage relationship. Activation of IK,r was not dependent on transient changes in intracellular Ca2+ concentration. Block of Ca2+ current by nisoldipine or nitrendipine did not prevent activation of IK,r. Peak IK,r was not decreased in cells when intracellular Ca2+ was strongly buffered with 1,2-bis(aminophenoxy)ethane-N,N,N',N'-tetraacetic acid. The activation curve for IK,r in atrial cells had a threshold of -40 mV, a half-point of -19 mV, and a slope factor of 5.2 mV. The activation curve for IK,s had a half-point of +24 mV and a slope factor of 15.7 mV. The peak tail currents of fully activated IK,s (21.1 pA/pF) and IK,r (2.53 pA/pF) are about two times that previously measured in guinea pig ventricular cells. This difference in current density may partly explain why action potentials of atrial cells are shorter than those of ventricular cells in guinea pig hearts.

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