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Abnormal cardiac Na(+) channel properties and QT heart rate adaptation in neonatal ankyrin(B) knockout mice.

Publication ,  Journal Article
Chauhan, VS; Tuvia, S; Buhusi, M; Bennett, V; Grant, AO
Published in: Circ Res
March 3, 2000

The cytoskeleton of the cardiomyocyte has been shown to modulate ion channel function. Cytoskeletal disruption in vitro alters Na(+) channel kinetics, producing a late Na(+) current that can prolong repolarization. This study describes the properties of the cardiac Na(+) channel and cardiac repolarization in neonatal mice lacking ankyrin(B), a cytoskeletal "adaptor" protein. Using whole-cell voltage clamp techniques, I(Na) density was lower in ankyrin(B)(-/-) ventricular myocytes than in wild-type (WT) myocytes (-307+/-26 versus -444+/-39 pA/pF, P<0.01). Ankyrin(B)(-/-) myocytes exhibited a hyperpolarizing shift in activation and inactivation kinetics compared with WT. Slower recovery from inactivation contributed to the negative shift in steady-state inactivation in ankyrin(B)(-/-). Single Na(+) channel mean open time was longer in ankyrin(B)(-/-) versus WT at test potentials (V(t)) of -40 mV (1.0+/-0.1 versus 0. 61+/-0.04 ms, P<0.05) and -50 mV (0.8+/-0.1 versus 0.39+/-0.05 ms, P<0.05). Ankyrin(B)(-/-) exhibited late single-channel openings at V(t) -40 and -50 mV, which were not seen in WT. Late I(Na) contributed to longer action potential durations measured at 90% repolarization (APD(90)) at 1 Hz stimulation in ankyrin(B)(-/-) compared with WT (354+/-26 versus 274+/-22 ms, P<0.05). From ECG recordings of neonatal mice, heart rates were slower in ankyrin(B)(-/-) than in WT (380+/-14 versus 434+/-13 bpm, P<0.01). Although the QT interval was similar in ankyrin(B)(-/-) and WT at physiological heart rates, QT-interval prolongation in response to heart rate deceleration was greater in ankyrin(B)(-/-). In conclusion, Na(+) channels in ankyrin(B)(-/-) display reduced I(Na) density and abnormal kinetics at the whole-cell and single-channel level that contribute to prolonged APD(90) and abnormal QT-rate adaptation.

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Published In

Circ Res

DOI

EISSN

1524-4571

Publication Date

March 3, 2000

Volume

86

Issue

4

Start / End Page

441 / 447

Location

United States

Related Subject Headings

  • Sodium Channels
  • Reference Values
  • Patch-Clamp Techniques
  • Myocardium
  • Mice, Knockout
  • Mice
  • Long QT Syndrome
  • Heart Rate
  • Electrocardiography
  • Cardiovascular System & Hematology
 

Citation

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Chauhan, V. S., Tuvia, S., Buhusi, M., Bennett, V., & Grant, A. O. (2000). Abnormal cardiac Na(+) channel properties and QT heart rate adaptation in neonatal ankyrin(B) knockout mice. Circ Res, 86(4), 441–447. https://doi.org/10.1161/01.res.86.4.441
Chauhan, V. S., S. Tuvia, M. Buhusi, V. Bennett, and A. O. Grant. “Abnormal cardiac Na(+) channel properties and QT heart rate adaptation in neonatal ankyrin(B) knockout mice.Circ Res 86, no. 4 (March 3, 2000): 441–47. https://doi.org/10.1161/01.res.86.4.441.
Chauhan VS, Tuvia S, Buhusi M, Bennett V, Grant AO. Abnormal cardiac Na(+) channel properties and QT heart rate adaptation in neonatal ankyrin(B) knockout mice. Circ Res. 2000 Mar 3;86(4):441–7.
Chauhan, V. S., et al. “Abnormal cardiac Na(+) channel properties and QT heart rate adaptation in neonatal ankyrin(B) knockout mice.Circ Res, vol. 86, no. 4, Mar. 2000, pp. 441–47. Pubmed, doi:10.1161/01.res.86.4.441.
Chauhan VS, Tuvia S, Buhusi M, Bennett V, Grant AO. Abnormal cardiac Na(+) channel properties and QT heart rate adaptation in neonatal ankyrin(B) knockout mice. Circ Res. 2000 Mar 3;86(4):441–447.

Published In

Circ Res

DOI

EISSN

1524-4571

Publication Date

March 3, 2000

Volume

86

Issue

4

Start / End Page

441 / 447

Location

United States

Related Subject Headings

  • Sodium Channels
  • Reference Values
  • Patch-Clamp Techniques
  • Myocardium
  • Mice, Knockout
  • Mice
  • Long QT Syndrome
  • Heart Rate
  • Electrocardiography
  • Cardiovascular System & Hematology