Role of slow delayed rectifier K+-current in QT prolongation in the alloxan-induced diabetic rabbit heart

The role of adrenergic and cholinergic stimulation in regulating the delayed outward K+ current (IK) was examined by using isolated guinea pig ventricular myocytes. Isoproterenol (ISO) stimulated IK in a reversible manner. Similar effects were seen by directly stimulating adenylate cyclase with forskolin (FSK). The responses to ISO and FSK were reversed by concurrent application of acetylcholine (ACh), but ACh alone did not affect IK. When a nonhydrolyzable analogue of guanosine 5'-triphosphate was introduced intracellularly, in the presence of extracellular ISO, IK was irreversibly stimulated. In cells pretreated with pertussis toxin the ACh response was blocked. These results suggest that autonomic regulation of IK is similar to that of the Ca2+ current and involves guanine nucleotide-binding proteins. This has important implications with respect to autonomic control of action potential duration and pacemaker activity in the heart.

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Presence and functional role of the rapidly activating delayed rectifier K+ current in left and right atria of adult mice

European Journal of Pharmacology ◽

10.1016/j.ejphar.2010.08.025 ◽

2010 ◽

Vol 649 (1-3) ◽

pp. 14-22 ◽

Cited By ~ 11

Author(s):

Hiroko Nakamura ◽

Wei-Guang Ding ◽

Mitsuru Sanada ◽

Kengo Maeda ◽

Hiromichi Kawai ◽

...

Keyword(s):

Functional Role ◽

Delayed Rectifier ◽

Adult Mice ◽

K Current ◽

Left And Right ◽

Right Atria

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06 Possible role of the ultra-rapid delayed rectifier potassium current (IKur) in action potential repolarisation in rabbit heart

Heart ◽

10.1136/hrt.2010.213496.6 ◽

2010 ◽

Vol 97 (1) ◽

pp. e2-e2

Author(s):

Y. Cui ◽

C. Wilson ◽

S. Turner ◽

S. Graham ◽

N. McMahon ◽

...

Keyword(s):

Action Potential ◽

Potassium Current ◽

Rabbit Heart ◽

Delayed Rectifier ◽

Delayed Rectifier Potassium Current

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Role of KCNQ1 in the Cell Swelling-Induced Enhancement of the Slowly Activating Delayed Rectifier K+ Current.

The Japanese Journal of Physiology ◽

10.2170/jjphysiol.52.31 ◽

2002 ◽

Vol 52 (1) ◽

pp. 31-39 ◽

Cited By ~ 16

Author(s):

Tomoyuki Kubota ◽

Minoru Horie ◽

Makoto Takano ◽

Hidetada Yoshida ◽

Hideo Otani ◽

...

Keyword(s):

Cell Swelling ◽

Delayed Rectifier ◽

K Current

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Transient outward and delayed rectifier currents in canine atrium: properties and role of isolation methods

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1996.270.6.h2157 ◽

1996 ◽

Vol 270 (6) ◽

pp. H2157-H2168 ◽

Cited By ~ 56

Author(s):

L. Yue ◽

J. Feng ◽

G. R. Li ◽

S. Nattel

Keyword(s):

Cell Voltage ◽

In Vivo Studies ◽

Delayed Rectifier ◽

Human Atrium ◽

Arterial Perfusion ◽

Outward Currents ◽

K Current

Although the dog is the principal species used for in vivo studies of atrial arrhythmias, little is known about currents governing canine atrial repolarization. Cells were isolated from dog atria by exposure to collagenase of tissue in vitro (“chunk cells”) and by arterial perfusion (“perfusion cells”). Whole cell voltage clamp revealed transient outward K+ current (Ito1), Ca(2+)-dependent Cl- current (Ito2), and delayed rectifier K+ current (IK). Ito1 recovered rapidly and showed little frequency dependence. Two components of IK were present as follows: a rapidly activating E-4031-sensitive current with marked inward recitification and a slower-activating E-4031-insensitive component. Ito1 and IK resembled corresponding currents previously described in human atrium. Transient outward currents were similar in chunk and perfusion cells, but IK was seen in 4% of chunk cells vs. 99% of perfusion cells (P < 0.001). Suppression of each identified current retarded canine action potential repolarization. We conclude that Ito1, Ito2, and both components of IK are present in dog atrium, IK is much more sensitive to the isolation method than Ito1 or Ito2, and the properties of two important repolarizing currents (Ito1 and IK) previously described in human atrium are similar to those in dog atrium.

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Characteristics of the delayed rectifier K current compared in myocytes isolated from the atrioventricular node and ventricle of the rabbit heart

Pflügers Archiv - European Journal of Physiology ◽

10.1007/bf02253834 ◽

1996 ◽

Vol 431 (5) ◽

pp. 713-722 ◽

Cited By ~ 33

Author(s):

F. C. Howarth ◽

Allan J. Levi ◽

Jules C. Hancox

Keyword(s):

Atrioventricular Node ◽

Rabbit Heart ◽

Delayed Rectifier ◽

K Current

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Regional differences in IK density in canine left ventricle: role of IK,s in electrical heterogeneity

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1995.268.2.h604 ◽

1995 ◽

Vol 268 (2) ◽

pp. H604-H613 ◽

Cited By ~ 6

Author(s):

G. A. Gintant

Keyword(s):

Regional Differences ◽

Left Ventricular ◽

Delayed Rectifier ◽

Activation Kinetics ◽

Whole Cell Patch Clamp ◽

K Current ◽

C And N ◽

Discernible Difference ◽

Epicardial Myocytes

Delayed rectifier K+ current (IK) was studied in isolated myocytes from canine left ventricular epicardium and midmyocardium using whole cell patch-clamp techniques. IK density during activation was greater in epicardial vs. midmyocardial myocytes [1.06 +/- 0.09 vs. 0.66 +/- 0.09 pA/pF (SE); P < 0.01] measured during 3-s depolarizing pulses to +25 mV. IK density was greater in epicardial myocytes at all times examined (range 150 ms to 3 s, +25 mV) and on termination of 3-s test pulses (potentials +5 to +65 mV). Greater IK density could not be explained by differences in activation kinetics or voltage dependence of activation. Two components of IK (IK,r and IK,s) have been described in guinea pig myocytes (Sanguinetti, M. C., and N. Jurkiewicz, J. Gen. Physiol. 96: 192–214, 1990). To assess whether differences in IK density could be ascribed to IK,r or IK,s, tail currents were fit to the sum of two decaying exponentials, with each component analogous to IK,s and IK,r based on sensitivity to E-4031 and rectification properties. Greater tail current density in epicardial myocytes was due to greater IK,s with no discernible difference in IK,r. These results suggest that regional differences in IK density in left ventricular epicardium are due to a larger IK,s component, which contributes to ventricular electrical heterogeneity and may reflect the differential expression of the IsK channel.

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IK of rabbit ventricle is composed of two currents: evidence for IKs

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1996.271.6.h2477 ◽

1996 ◽

Vol 271 (6) ◽

pp. H2477-H2489 ◽

Cited By ~ 17

Author(s):

J. J. Salata ◽

N. K. Jurkiewicz ◽

B. Jow ◽

K. Folander ◽

P. J. Guinosso ◽

...

Keyword(s):

Ventricular Myocytes ◽

Rabbit Heart ◽

Northern Analysis ◽

Delayed Rectifier ◽

Human Genes ◽

Voltage Dependent ◽

Slope Factor ◽

K Current ◽

A Subunit ◽

K Concentration

The delayed rectifier K+ current (IK) in rabbit heart has long been thought to consist of only a single, rapidly activating, dofetilide-sensitive current, IKr. However, we find that IK of rabbit ventricular myocytes actually consists of both rapid and slow components, IKr and IKs, respectively, that can be isolated pharmacologically. Thus, after complete blockade of IKr with dofetilide, the remaining current, IKs, is homogeneous as judged by an envelope of tails test. IKs activates and deactivates slowly, continues to activate during sustained depolarizations, has a half-activation potential of 7.0 +/- 0.8 mV and slope factor of 11.0 +/- 0.7 mV, reverses at -77.2 +/- 1.3 mV (extracellular K+ concentration = 4 mM), is increased by removing extracellular K+, and is enhanced by isoproterenol and stocked by azimilide. Northern analysis demonstrates that the minK (IsK) gene, which encodes a subunit of the channel that underlies the IKs current, is expressed in rabbit heart. Expression of the rabbit protein in Xenopus oocytes elicits a slowly activating, voltage-dependent current, IsK, similar to those expressed previously from mouse, rat, guinea pig, and human genes. The results demonstrate that IKs is present in rabbit ventricle and therefore contributes to cardiac repolarization in this species.

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