DOI: 10.1085/jgp.113.4.581. Distinct Transient Outward Potassium Current (Ito) Phenotypes and Distribution of Fast-inactivating Potassium Channel Alpha Subunits in Ferret Left Ventricular Myocytes

Distinct Transient Outward Potassium Current (Ito) Phenotypes and Distribution of Fast-inactivating Potassium Channel Alpha Subunits in Ferret Left Ventricular Myocytes

10.1085/jgp.113.4.581

Crossref journal-article

Rockefeller University Press

The Journal of General Physiology (291)

Abstract

The biophysical characteristics and α subunits underlying calcium-independent transient outward potassium current (Ito) phenotypes expressed in ferret left ventricular epicardial (LV epi) and endocardial (LV endo) myocytes were analyzed using patch clamp, fluorescent in situ hybridization (FISH), and immunofluorescent (IF) techniques. Two distinct Ito phenotypes were measured (21–22°C) in the majority of LV epi and LV endo myocytes studied. The two Ito phenotypes displayed marked differences in peak current densities, activation thresholds, inactivation characteristics, and recovery kinetics. Ito,epi recovered rapidly [τrec, −70 mV = 51 ± 3 ms] with minimal cumulative inactivation, while Ito,endo recovered slowly [τrec, −70 mV = 3,002 ± 447 ms] with marked cumulative inactivation. Heteropoda toxin 2 (150 nM) blocked Ito,epi in a voltage-dependent manner, but had no effect on Ito,endo. Parallel FISH and IF measurements conducted on isolated LV epi and LV endo myocytes demonstrated that Kv1.4, Kv4.2, and Kv4.3 α subunit expression in LV myocyte types was quite heterogenous: (a) Kv4.2 and Kv4.3 were more predominantly expressed in LV epi than LV endo myocytes, and (b) Kv1.4 was expressed in the majority of LV endo myocytes but was essentially absent in LV epi myocytes. In combination with previous measurements on recovery kinetics (Kv1.4, slow; Kv4.2/4.3, relatively rapid) and Heteropoda toxin block (Kv1.4, insensitive; Kv4.2, sensitive), our results strongly support the hypothesis that, in ferret heart, Kv4.2/Kv4.3 and Kv1.4 α subunits, respectively, are the molecular substrates underlying the Ito,epi and Ito,endo phenotypes. FISH and IF measurements were also conducted on ferret ventricular tissue sections. The three Ito α subunits again showed distinct patterns of distribution: (a) Kv1.4 was localized primarily to the apical portion of the LV septum, LV endocardium, and approximate inner 75% of the LV free wall; (b) Kv4.2 was localized primarily to the right ventricular free wall, epicardial layers of the LV, and base of the heart; and (c) Kv4.3 was localized primarily to epicardial layers of the LV apex and diffusely distributed in the LV free wall and septum. Therefore, in intact ventricular tissue, a heterogeneous distribution of candidate Ito α subunits not only exists from LV epicardium to endocardium but also from apex to base.

Bibliography

Brahmajothi, M. V., Campbell, D. L., Rasmusson, R. L., Morales, M. J., Trimmer, J. S., Nerbonne, J. M., & Strauss, H. C. (1999). Distinct Transient Outward Potassium Current (Ito) Phenotypes and Distribution of Fast-inactivating Potassium Channel Alpha Subunits in Ferret Left Ventricular Myocytes. The Journal of General Physiology, 113(4), 581â600.

Authors 7

Mulugu V. Brahmajothi (first)
Donald L. Campbell (additional)
Randall L. Rasmusson (additional)
Michael J. Morales (additional)
James S. Trimmer (additional)
Jeanne M. Nerbonne (additional)
Harold C. Strauss (additional)

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 12:50 p.m.)
Deposited	2 years, 1 month ago (July 26, 2023, 2:23 p.m.)
Indexed	11 months, 3 weeks ago (Sept. 7, 2024, 4:48 p.m.)
Issued	26 years, 5 months ago (April 1, 1999)
Published	26 years, 5 months ago (April 1, 1999)
Published Online	26 years, 5 months ago (April 1, 1999)
Published Print	26 years, 5 months ago (April 1, 1999)

Funders 0

None

BibTeX

@article{Brahmajothi_1999, title={Distinct Transient Outward Potassium Current (Ito) Phenotypes and Distribution of Fast-inactivating Potassium Channel Alpha Subunits in Ferret Left Ventricular Myocytes}, volume={113}, ISSN={1540-7748}, url={http://dx.doi.org/10.1085/jgp.113.4.581}, DOI={10.1085/jgp.113.4.581}, number={4}, journal={The Journal of General Physiology}, publisher={Rockefeller University Press}, author={Brahmajothi, Mulugu V. and Campbell, Donald L. and Rasmusson, Randall L. and Morales, Michael J. and Trimmer, James S. and Nerbonne, Jeanne M. and Strauss, Harold C.}, year={1999}, month=apr, pages={581–600} }

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  "abstract": "<jats:p>The biophysical characteristics and \u03b1 subunits underlying calcium-independent transient outward potassium current (Ito) phenotypes expressed in ferret left ventricular epicardial (LV epi) and endocardial (LV endo) myocytes were analyzed using patch clamp, fluorescent in situ hybridization (FISH), and immunofluorescent (IF) techniques. Two distinct Ito phenotypes were measured (21\u201322\u00b0C) in the majority of LV epi and LV endo myocytes studied. The two Ito phenotypes displayed marked differences in peak current densities, activation thresholds, inactivation characteristics, and recovery kinetics. Ito,epi recovered rapidly [\u03c4rec, \u221270 mV = 51 \u00b1 3 ms] with minimal cumulative inactivation, while Ito,endo recovered slowly [\u03c4rec, \u221270 mV = 3,002 \u00b1 447 ms] with marked cumulative inactivation. Heteropoda toxin 2 (150 nM) blocked Ito,epi in a voltage-dependent manner, but had no effect on Ito,endo. Parallel FISH and IF measurements conducted on isolated LV epi and LV endo myocytes demonstrated that Kv1.4, Kv4.2, and Kv4.3 \u03b1 subunit expression in LV myocyte types was quite heterogenous: (a) Kv4.2 and Kv4.3 were more predominantly expressed in LV epi than LV endo myocytes, and (b) Kv1.4 was expressed in the majority of LV endo myocytes but was essentially absent in LV epi myocytes. In combination with previous measurements on recovery kinetics (Kv1.4, slow; Kv4.2/4.3, relatively rapid) and Heteropoda toxin block (Kv1.4, insensitive; Kv4.2, sensitive), our results strongly support the hypothesis that, in ferret heart, Kv4.2/Kv4.3 and Kv1.4 \u03b1 subunits, respectively, are the molecular substrates underlying the Ito,epi and Ito,endo phenotypes. FISH and IF measurements were also conducted on ferret ventricular tissue sections. The three Ito \u03b1 subunits again showed distinct patterns of distribution: (a) Kv1.4 was localized primarily to the apical portion of the LV septum, LV endocardium, and approximate inner 75% of the LV free wall; (b) Kv4.2 was localized primarily to the right ventricular free wall, epicardial layers of the LV, and base of the heart; and (c) Kv4.3 was localized primarily to epicardial layers of the LV apex and diffusely distributed in the LV free wall and septum. Therefore, in intact ventricular tissue, a heterogeneous distribution of candidate Ito \u03b1 subunits not only exists from LV epicardium to endocardium but also from apex to base.</jats:p>",
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