What is the clinical evidence from this study?

Study design: Other. Intervention: 4-aminopyridine (4-AP). Primary outcome: Inhibition of K(DR) channels and voltage dependence of activation.

What question did this study set out to answer?

To identify the molecular composition of vascular delayed rectifier potassium channels in rabbit portal vein myocytes and characterize their inhibition by 4-aminopyridine.

November 23, 2001Circulation ResearchOpen Access

Heteromultimeric Kv1.2-Kv1.5 Channels Underlie 4-Aminopyridine-Sensitive Delayed Rectifier K+Current of Rabbit Vascular Myocytes

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Key result

4-aminopyridine inhibits vascular delayed rectifier K+ channels via an open-state block mechanism, revealing that the dominant channel complex involves heteromultimeric Kv1.2 and Kv1.5 subunits.

Population

Rabbit portal vein (RPV) myocytes and mammalian cells expressing cloned Kv1.5 and/or Kv1.2 subunits

Design

Preclinical

Authors

PKPaul M. KerrMacEwan University OCOdile Clément‐ChomienneUniversité Paris-Sud KTKevin S. ThorneloeBJC HealthCare

Discussion

Member takes

Implication

No immediate clinical implications; extends molecular identification of vascular K(DR) subunits for future mechanistic studies.

Key Points

To identify the molecular composition of vascular delayed rectifier potassium channels in rabbit portal vein myocytes and characterize their inhibition by 4-aminopyridine.
Measured 4-aminopyridine inhibition of native delayed rectifier potassium currents in rabbit portal vein myocytes using whole-cell patch-clamp electrophysiology.
Cloned Kv1.2 and Kv1.5 subunits from rabbit portal vein and expressed them as homotetramers, coexpressed mixtures, or tandem heterotetrameric [Kv1.5/Kv1.2]2 constructs in mammalian cells for comparative biophysical analysis.
4-Aminopyridine inhibited native delayed rectifier currents through an open-state block mechanism with drug trapping upon closure, causing a positive shift in activation voltage dependence and reducing mean open time.
Native currents displayed an activation shift upon 4-aminopyridine exposure matching Kv1.2 and heterotetrameric [Kv1.5/Kv1.2]2 channels but not Kv1.5 homotetramers, while showing insensitivity to charybdotoxin, identifying the native complex as a Kv1.2-Kv1.5 heteromultimer.

Structured PICO

Population

Rabbit portal vein (RPV) myocytes and mammalian cells expressing cloned Kv1.5 and/or Kv1.2 subunits

Intervention

4-aminopyridine (4-AP)

Outcome

Electrophysiological characteristics of K(DR) inhibition (voltage dependence of activation, mean open time, relief of block)surrogate

The study identifies that the dominant form of vascular delayed rectifier K+ channels in rabbit portal vein involves a heteromultimeric association of Kv1.2 and Kv1.5 subunits.

Cite This Study

Kerr et al. (2001) studied this question. 4-aminopyridine (4-AP) was evaluated on Inhibition of K(DR) channels and voltage dependence of activation. 4-aminopyridine inhibits vascular delayed rectifier K+ channels via an open-state block mechanism, revealing that the dominant channel complex involves heteromultimeric Kv1.2 and Kv1.5 subunits.

synapsesocial.com/papers/6a6bd06426cff2e2f6f4832b https://doi.org/10.1161/hh2301.100803

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November 23, 2001Circulation ResearchOpen Access

Heteromultimeric Kv1.2-Kv1.5 Channels Underlie 4-Aminopyridine-Sensitive Delayed Rectifier K+Current of Rabbit Vascular Myocytes

View Full Paper

Ask AI

Bookmark

Key result

4-aminopyridine inhibits vascular delayed rectifier K+ channels via an open-state block mechanism, revealing that the dominant channel complex involves heteromultimeric Kv1.2 and Kv1.5 subunits.

Population

Rabbit portal vein (RPV) myocytes and mammalian cells expressing cloned Kv1.5 and/or Kv1.2 subunits

Design

Preclinical

Authors

PKPaul M. KerrMacEwan University OCOdile Clément‐ChomienneUniversité Paris-Sud KTKevin S. ThorneloeBJC HealthCare

Discussion

Member takes

Implication

No immediate clinical implications; extends molecular identification of vascular K(DR) subunits for future mechanistic studies.

Key Points

To identify the molecular composition of vascular delayed rectifier potassium channels in rabbit portal vein myocytes and characterize their inhibition by 4-aminopyridine.
Measured 4-aminopyridine inhibition of native delayed rectifier potassium currents in rabbit portal vein myocytes using whole-cell patch-clamp electrophysiology.
Cloned Kv1.2 and Kv1.5 subunits from rabbit portal vein and expressed them as homotetramers, coexpressed mixtures, or tandem heterotetrameric [Kv1.5/Kv1.2]2 constructs in mammalian cells for comparative biophysical analysis.
4-Aminopyridine inhibited native delayed rectifier currents through an open-state block mechanism with drug trapping upon closure, causing a positive shift in activation voltage dependence and reducing mean open time.
Native currents displayed an activation shift upon 4-aminopyridine exposure matching Kv1.2 and heterotetrameric [Kv1.5/Kv1.2]2 channels but not Kv1.5 homotetramers, while showing insensitivity to charybdotoxin, identifying the native complex as a Kv1.2-Kv1.5 heteromultimer.

Structured PICO

Population

Rabbit portal vein (RPV) myocytes and mammalian cells expressing cloned Kv1.5 and/or Kv1.2 subunits

Intervention

4-aminopyridine (4-AP)

Outcome

Electrophysiological characteristics of K(DR) inhibition (voltage dependence of activation, mean open time, relief of block)surrogate

The study identifies that the dominant form of vascular delayed rectifier K+ channels in rabbit portal vein involves a heteromultimeric association of Kv1.2 and Kv1.5 subunits.

Cite This Study

synapsesocial.com/papers/6a6bd06426cff2e2f6f4832b https://doi.org/10.1161/hh2301.100803

Also Consider

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