The min K channel underlies the cardiac potassium current IKs and mediates species-specific responses to protein kinase C

Michael D. Varnum, Andreas E. Busch, Chris T. Bond, James Maylie, John Adelman

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

A clone encoding the guinea pig (gp) min K potassium channel was isolated and expressed in Xenopus oocytes. The currents, gpIsK, exhibit many of the electrophysiological and pharmacological properties characteristic of gpIKs, the slow component of the delayed rectifier potassium conductance in guinea pig cardiac myocytes. Depolarizing commands evoke outward potassium currents that activate slowly, with time constants on the order of seconds. The currents are blocked by the class III antiarrhythmic compound clofilium but not by the sotalol derivative E4031 or low concentrations of lanthanum. Like IKs in guinea pig myocytes, gpIsK is modulated by stimulation of protein kinase A and protein kinase C (PKC). In contrast to rat and mouse IsK, which are decreased upon stimulation of PKC, myocyte IK and gpIsK in oocytes are increased after PKC stimulation. Substitution of an asparagine residue at position 102 by serine (N102S), the residue found in the analogous position of the mouse and rat min K proteins, results in decreased gpIsK in response to PKC stimulation. These results support the hypothesis that the min K protein underlies the slow component of the delayed rectifier potassium current in ventricular myocytes and account for the species-specific responses to stimulation of PKC.

Original languageEnglish (US)
Pages (from-to)11528-11532
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume90
Issue number24
StatePublished - Dec 15 1993

Fingerprint

Protein Kinase C
Potassium
Muscle Cells
Guinea Pigs
Oocytes
Sotalol
Lanthanum
Asparagine
Potassium Channels
Xenopus
Cyclic AMP-Dependent Protein Kinases
Cardiac Myocytes
Serine
Clone Cells
Pharmacology

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

The min K channel underlies the cardiac potassium current IKs and mediates species-specific responses to protein kinase C. / Varnum, Michael D.; Busch, Andreas E.; Bond, Chris T.; Maylie, James; Adelman, John.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 90, No. 24, 15.12.1993, p. 11528-11532.

Research output: Contribution to journalArticle

@article{67e75ef05c4f4086adbd4037a632eb4a,
title = "The min K channel underlies the cardiac potassium current IKs and mediates species-specific responses to protein kinase C",
abstract = "A clone encoding the guinea pig (gp) min K potassium channel was isolated and expressed in Xenopus oocytes. The currents, gpIsK, exhibit many of the electrophysiological and pharmacological properties characteristic of gpIKs, the slow component of the delayed rectifier potassium conductance in guinea pig cardiac myocytes. Depolarizing commands evoke outward potassium currents that activate slowly, with time constants on the order of seconds. The currents are blocked by the class III antiarrhythmic compound clofilium but not by the sotalol derivative E4031 or low concentrations of lanthanum. Like IKs in guinea pig myocytes, gpIsK is modulated by stimulation of protein kinase A and protein kinase C (PKC). In contrast to rat and mouse IsK, which are decreased upon stimulation of PKC, myocyte IK and gpIsK in oocytes are increased after PKC stimulation. Substitution of an asparagine residue at position 102 by serine (N102S), the residue found in the analogous position of the mouse and rat min K proteins, results in decreased gpIsK in response to PKC stimulation. These results support the hypothesis that the min K protein underlies the slow component of the delayed rectifier potassium current in ventricular myocytes and account for the species-specific responses to stimulation of PKC.",
author = "Varnum, {Michael D.} and Busch, {Andreas E.} and Bond, {Chris T.} and James Maylie and John Adelman",
year = "1993",
month = "12",
day = "15",
language = "English (US)",
volume = "90",
pages = "11528--11532",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "24",

}

TY - JOUR

T1 - The min K channel underlies the cardiac potassium current IKs and mediates species-specific responses to protein kinase C

AU - Varnum, Michael D.

AU - Busch, Andreas E.

AU - Bond, Chris T.

AU - Maylie, James

AU - Adelman, John

PY - 1993/12/15

Y1 - 1993/12/15

N2 - A clone encoding the guinea pig (gp) min K potassium channel was isolated and expressed in Xenopus oocytes. The currents, gpIsK, exhibit many of the electrophysiological and pharmacological properties characteristic of gpIKs, the slow component of the delayed rectifier potassium conductance in guinea pig cardiac myocytes. Depolarizing commands evoke outward potassium currents that activate slowly, with time constants on the order of seconds. The currents are blocked by the class III antiarrhythmic compound clofilium but not by the sotalol derivative E4031 or low concentrations of lanthanum. Like IKs in guinea pig myocytes, gpIsK is modulated by stimulation of protein kinase A and protein kinase C (PKC). In contrast to rat and mouse IsK, which are decreased upon stimulation of PKC, myocyte IK and gpIsK in oocytes are increased after PKC stimulation. Substitution of an asparagine residue at position 102 by serine (N102S), the residue found in the analogous position of the mouse and rat min K proteins, results in decreased gpIsK in response to PKC stimulation. These results support the hypothesis that the min K protein underlies the slow component of the delayed rectifier potassium current in ventricular myocytes and account for the species-specific responses to stimulation of PKC.

AB - A clone encoding the guinea pig (gp) min K potassium channel was isolated and expressed in Xenopus oocytes. The currents, gpIsK, exhibit many of the electrophysiological and pharmacological properties characteristic of gpIKs, the slow component of the delayed rectifier potassium conductance in guinea pig cardiac myocytes. Depolarizing commands evoke outward potassium currents that activate slowly, with time constants on the order of seconds. The currents are blocked by the class III antiarrhythmic compound clofilium but not by the sotalol derivative E4031 or low concentrations of lanthanum. Like IKs in guinea pig myocytes, gpIsK is modulated by stimulation of protein kinase A and protein kinase C (PKC). In contrast to rat and mouse IsK, which are decreased upon stimulation of PKC, myocyte IK and gpIsK in oocytes are increased after PKC stimulation. Substitution of an asparagine residue at position 102 by serine (N102S), the residue found in the analogous position of the mouse and rat min K proteins, results in decreased gpIsK in response to PKC stimulation. These results support the hypothesis that the min K protein underlies the slow component of the delayed rectifier potassium current in ventricular myocytes and account for the species-specific responses to stimulation of PKC.

UR - http://www.scopus.com/inward/record.url?scp=0027142051&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027142051&partnerID=8YFLogxK

M3 - Article

C2 - 8265583

AN - SCOPUS:0027142051

VL - 90

SP - 11528

EP - 11532

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 24

ER -