Deleting the accessory subunit KChIP2 results in loss of I(to,f) and increased I(K,slow) that maintains normal action potential configuration

Morten B Thomsen; Eugene A Sosunov; Evgeny P Anyukhovsky; Nazira Ozgen; Penelope A Boyden; Michael R Rosen

doi:10.1016/j.hrthm.2008.11.023

Deleting the accessory subunit KChIP2 results in loss of I(to,f) and increased I(K,slow) that maintains normal action potential configuration

Morten B Thomsen, Eugene A Sosunov, Evgeny P Anyukhovsky, Nazira Ozgen, Penelope A Boyden, Michael R Rosen

Physiology of circulation, kidney and lung

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

29 Citationer (Scopus)

Abstract

Udgivelsesdato: 2009-Mar

Originalsprog	Engelsk
Tidsskrift	Heart Rhythm
Vol/bind	6
Udgave nummer	3
Sider (fra-til)	370-7
Antal sider	7
ISSN	1547-5271
DOI	https://doi.org/10.1016/j.hrthm.2008.11.023
Status	Udgivet - 2008

Bibliografisk note

Keywords: Action Potentials; Animals; Electrophysiologic Techniques, Cardiac; Heart Ventricles; Kv Channel-Interacting Proteins; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Microelectrodes; Myocytes, Cardiac; Patch-Clamp Techniques; Potassium Channels, Voltage-Gated; Reverse Transcriptase Polymerase Chain Reaction

Adgang til dokumentet

10.1016/j.hrthm.2008.11.023

Citationsformater

Deleting the accessory subunit KChIP2 results in loss of I(to,f) and increased I(K,slow) that maintains normal action potential configuration. / Thomsen, Morten B; Sosunov, Eugene A; Anyukhovsky, Evgeny P; Ozgen, Nazira; Boyden, Penelope A; Rosen, Michael R.

I: Heart Rhythm, Bind 6, Nr. 3, 2008, s. 370-7.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

@article{656b7860368011df8ed1000ea68e967b,

title = "Deleting the accessory subunit KChIP2 results in loss of I(to,f) and increased I(K,slow) that maintains normal action potential configuration",

abstract = "BACKGROUND: Four voltage-gated potassium currents, I(to,f) (K(V)4.2), I(to,s) (K(V)1.4), I(K,slow) (K(V)1.5+K(V)2.1), and I(SS) (TASK1), govern murine ventricular repolarization. Although the accessory subunit KChIP2 influences I(to,f) expression, in preliminary experiments we found that action potential duration (APD) is maintained in KChIP2 knockout mice. OBJECTIVE: We tested the role of KChIP2 in regulating APD and studied the underlying ionic currents. METHODS: We used microelectrode techniques, whole-cell patch clamp studies, and real-time polymerase chain reaction amplification to characterize ventricular repolarization and its determinants in wild-type and KChIP2(-/-) mice. RESULTS: Despite comparable baseline action potentials, APD was more markedly prolonged by 4-aminopyridine (4-AP) in KChIP2(-/-) preparations. Peak K(+) current densities were similar in wild-type and KChIP2(-/-) cells (mean +/- SEM I(P): 28.3 +/- 2 (n = 27) vs. 29.2 +/- 2 pA/pF (n = 24), respectively; P > .05). Heteropodatoxin-2 (HpTx-2, 1 microM) had no effect on current amplitude in KChIP2(-/-) myocytes. The current fractions sensitive to 4-AP (50 microM and 1 mM) were larger in KChIP2(-/-) than wild-type (P < .05). Real-time polymerase chain reaction showed absence of KChIP2 and increased K(V)1.5 expression in KChIP2(-/-) ventricular myocardium. CONCLUSION: KChIP2 deficiency eliminated HpTx-2-sensitive I(to,f), but had little impact on total APD, secondary to upregulation of 4-AP-sensitive I(K,slow) in association with increased K(V)1.5 expression. There is increased sensitivity to 4-AP-mediated APD prolongation in KChIP2(-/-). Thus, KChIP2 seems important for murine repolarization in circumstances of reduced repolarization reserve.",

author = "Thomsen, {Morten B} and Sosunov, {Eugene A} and Anyukhovsky, {Evgeny P} and Nazira Ozgen and Boyden, {Penelope A} and Rosen, {Michael R}",

note = "Keywords: Action Potentials; Animals; Electrophysiologic Techniques, Cardiac; Heart Ventricles; Kv Channel-Interacting Proteins; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Microelectrodes; Myocytes, Cardiac; Patch-Clamp Techniques; Potassium Channels, Voltage-Gated; Reverse Transcriptase Polymerase Chain Reaction",

year = "2008",

doi = "10.1016/j.hrthm.2008.11.023",

language = "English",

volume = "6",

pages = "370--7",

journal = "Heart Rhythm",

issn = "1547-5271",

publisher = "Elsevier",

number = "3",

}

TY - JOUR

T1 - Deleting the accessory subunit KChIP2 results in loss of I(to,f) and increased I(K,slow) that maintains normal action potential configuration

AU - Thomsen, Morten B

AU - Sosunov, Eugene A

AU - Anyukhovsky, Evgeny P

AU - Ozgen, Nazira

AU - Boyden, Penelope A

AU - Rosen, Michael R

N1 - Keywords: Action Potentials; Animals; Electrophysiologic Techniques, Cardiac; Heart Ventricles; Kv Channel-Interacting Proteins; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Microelectrodes; Myocytes, Cardiac; Patch-Clamp Techniques; Potassium Channels, Voltage-Gated; Reverse Transcriptase Polymerase Chain Reaction

PY - 2008

Y1 - 2008

N2 - BACKGROUND: Four voltage-gated potassium currents, I(to,f) (K(V)4.2), I(to,s) (K(V)1.4), I(K,slow) (K(V)1.5+K(V)2.1), and I(SS) (TASK1), govern murine ventricular repolarization. Although the accessory subunit KChIP2 influences I(to,f) expression, in preliminary experiments we found that action potential duration (APD) is maintained in KChIP2 knockout mice. OBJECTIVE: We tested the role of KChIP2 in regulating APD and studied the underlying ionic currents. METHODS: We used microelectrode techniques, whole-cell patch clamp studies, and real-time polymerase chain reaction amplification to characterize ventricular repolarization and its determinants in wild-type and KChIP2(-/-) mice. RESULTS: Despite comparable baseline action potentials, APD was more markedly prolonged by 4-aminopyridine (4-AP) in KChIP2(-/-) preparations. Peak K(+) current densities were similar in wild-type and KChIP2(-/-) cells (mean +/- SEM I(P): 28.3 +/- 2 (n = 27) vs. 29.2 +/- 2 pA/pF (n = 24), respectively; P > .05). Heteropodatoxin-2 (HpTx-2, 1 microM) had no effect on current amplitude in KChIP2(-/-) myocytes. The current fractions sensitive to 4-AP (50 microM and 1 mM) were larger in KChIP2(-/-) than wild-type (P < .05). Real-time polymerase chain reaction showed absence of KChIP2 and increased K(V)1.5 expression in KChIP2(-/-) ventricular myocardium. CONCLUSION: KChIP2 deficiency eliminated HpTx-2-sensitive I(to,f), but had little impact on total APD, secondary to upregulation of 4-AP-sensitive I(K,slow) in association with increased K(V)1.5 expression. There is increased sensitivity to 4-AP-mediated APD prolongation in KChIP2(-/-). Thus, KChIP2 seems important for murine repolarization in circumstances of reduced repolarization reserve.

AB - BACKGROUND: Four voltage-gated potassium currents, I(to,f) (K(V)4.2), I(to,s) (K(V)1.4), I(K,slow) (K(V)1.5+K(V)2.1), and I(SS) (TASK1), govern murine ventricular repolarization. Although the accessory subunit KChIP2 influences I(to,f) expression, in preliminary experiments we found that action potential duration (APD) is maintained in KChIP2 knockout mice. OBJECTIVE: We tested the role of KChIP2 in regulating APD and studied the underlying ionic currents. METHODS: We used microelectrode techniques, whole-cell patch clamp studies, and real-time polymerase chain reaction amplification to characterize ventricular repolarization and its determinants in wild-type and KChIP2(-/-) mice. RESULTS: Despite comparable baseline action potentials, APD was more markedly prolonged by 4-aminopyridine (4-AP) in KChIP2(-/-) preparations. Peak K(+) current densities were similar in wild-type and KChIP2(-/-) cells (mean +/- SEM I(P): 28.3 +/- 2 (n = 27) vs. 29.2 +/- 2 pA/pF (n = 24), respectively; P > .05). Heteropodatoxin-2 (HpTx-2, 1 microM) had no effect on current amplitude in KChIP2(-/-) myocytes. The current fractions sensitive to 4-AP (50 microM and 1 mM) were larger in KChIP2(-/-) than wild-type (P < .05). Real-time polymerase chain reaction showed absence of KChIP2 and increased K(V)1.5 expression in KChIP2(-/-) ventricular myocardium. CONCLUSION: KChIP2 deficiency eliminated HpTx-2-sensitive I(to,f), but had little impact on total APD, secondary to upregulation of 4-AP-sensitive I(K,slow) in association with increased K(V)1.5 expression. There is increased sensitivity to 4-AP-mediated APD prolongation in KChIP2(-/-). Thus, KChIP2 seems important for murine repolarization in circumstances of reduced repolarization reserve.

U2 - 10.1016/j.hrthm.2008.11.023

DO - 10.1016/j.hrthm.2008.11.023

M3 - Journal article

C2 - 19251214

VL - 6

SP - 370

EP - 377

JO - Heart Rhythm

JF - Heart Rhythm

SN - 1547-5271

IS - 3

ER -