Slowly Recovering Cardiac Sodium Current in Rat Ventricular Myocytes: Effects of Conditioning Duration and Recovery Potential

GREGG S. SHANDER, Zheng Fan, JONATHAN C. MAKIELSKI

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Slow Recovery of INa. introduction: Recovery of the Na channel from inactivation is essential to the normal conduction and refractoriness of the myocardium. In addition to fast recovery, occurring within several milliseconds at hyperpolarized potentials, a component of the current exhibits slow recovery occurring over hundreds of milliseconds. Long conditioning depolarizations potentiate slow recovery. Methods and Results: This study was designed to test conditioning durations (tc) between 0.25 and 4 seconds (s) as to whether recovery was slowed by an effect on the fast (τt) and slow (τs) time constants of recovery, the relative amplitude of the slow component (As), or both. We studied Na channel recovery at ‐150 mV from inactivation using whole cell voltage clamp of rat ventricular cells at 23°C using a two‐pulse recovery protocol. Longer conditioning durations dramatically increased As, (from 12% for tc= 500 msec to 37% for tc= 4(MM) msec, P < 0.01). Neither τt (6 vs 5 msec) nor τs, (115 vs 140 msec) were significantly affected. In a second set of experiments, the recovery potential was depolarized to a potential at which the sodium current was 70% available (≅‐105 mV). This recovery potential had no significant effect on As, but both τf and τs were significantly slower (e.g., at tc= 2s, τs= 147 msec and As, = 28% at Vr= ‐150 mV, and τs, = 456 msec and As, = 29% at Vr, ≅ ‐105 mV). In addition, a 1‐ to 2‐msec lag in the onset of recovery was prominent at the depolarized recovery potentials. Conclusions: Our results support a model for slow recovery where conditioning duration determines entry into an inactivated state from which Na channels recover slowly, and recovery potential determines the rate of recovery from this state. A kinetic scheme with at least three inactivated states is proposed. These results also have implications for cardiac excitability under conditions, such as ischemia, where membranes are depolarized.

Original languageEnglish (US)
Pages (from-to)786-795
Number of pages10
JournalJournal of Cardiovascular Electrophysiology
Volume6
Issue number10
DOIs
StatePublished - Jan 1 1995
Externally publishedYes

Fingerprint

Muscle Cells
Sodium
Myocardium
Ischemia
Membranes

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Slowly Recovering Cardiac Sodium Current in Rat Ventricular Myocytes : Effects of Conditioning Duration and Recovery Potential. / SHANDER, GREGG S.; Fan, Zheng; MAKIELSKI, JONATHAN C.

In: Journal of Cardiovascular Electrophysiology, Vol. 6, No. 10, 01.01.1995, p. 786-795.

Research output: Contribution to journalArticle

@article{7d414332030549919a127a7f7fedf318,
title = "Slowly Recovering Cardiac Sodium Current in Rat Ventricular Myocytes: Effects of Conditioning Duration and Recovery Potential",
abstract = "Slow Recovery of INa. introduction: Recovery of the Na channel from inactivation is essential to the normal conduction and refractoriness of the myocardium. In addition to fast recovery, occurring within several milliseconds at hyperpolarized potentials, a component of the current exhibits slow recovery occurring over hundreds of milliseconds. Long conditioning depolarizations potentiate slow recovery. Methods and Results: This study was designed to test conditioning durations (tc) between 0.25 and 4 seconds (s) as to whether recovery was slowed by an effect on the fast (τt) and slow (τs) time constants of recovery, the relative amplitude of the slow component (As), or both. We studied Na channel recovery at ‐150 mV from inactivation using whole cell voltage clamp of rat ventricular cells at 23°C using a two‐pulse recovery protocol. Longer conditioning durations dramatically increased As, (from 12{\%} for tc= 500 msec to 37{\%} for tc= 4(MM) msec, P < 0.01). Neither τt (6 vs 5 msec) nor τs, (115 vs 140 msec) were significantly affected. In a second set of experiments, the recovery potential was depolarized to a potential at which the sodium current was 70{\%} available (≅‐105 mV). This recovery potential had no significant effect on As, but both τf and τs were significantly slower (e.g., at tc= 2s, τs= 147 msec and As, = 28{\%} at Vr= ‐150 mV, and τs, = 456 msec and As, = 29{\%} at Vr, ≅ ‐105 mV). In addition, a 1‐ to 2‐msec lag in the onset of recovery was prominent at the depolarized recovery potentials. Conclusions: Our results support a model for slow recovery where conditioning duration determines entry into an inactivated state from which Na channels recover slowly, and recovery potential determines the rate of recovery from this state. A kinetic scheme with at least three inactivated states is proposed. These results also have implications for cardiac excitability under conditions, such as ischemia, where membranes are depolarized.",
author = "SHANDER, {GREGG S.} and Zheng Fan and MAKIELSKI, {JONATHAN C.}",
year = "1995",
month = "1",
day = "1",
doi = "10.1111/j.1540-8167.1995.tb00355.x",
language = "English (US)",
volume = "6",
pages = "786--795",
journal = "Journal of Cardiovascular Electrophysiology",
issn = "1045-3873",
publisher = "Wiley-Blackwell",
number = "10",

}

TY - JOUR

T1 - Slowly Recovering Cardiac Sodium Current in Rat Ventricular Myocytes

T2 - Effects of Conditioning Duration and Recovery Potential

AU - SHANDER, GREGG S.

AU - Fan, Zheng

AU - MAKIELSKI, JONATHAN C.

PY - 1995/1/1

Y1 - 1995/1/1

N2 - Slow Recovery of INa. introduction: Recovery of the Na channel from inactivation is essential to the normal conduction and refractoriness of the myocardium. In addition to fast recovery, occurring within several milliseconds at hyperpolarized potentials, a component of the current exhibits slow recovery occurring over hundreds of milliseconds. Long conditioning depolarizations potentiate slow recovery. Methods and Results: This study was designed to test conditioning durations (tc) between 0.25 and 4 seconds (s) as to whether recovery was slowed by an effect on the fast (τt) and slow (τs) time constants of recovery, the relative amplitude of the slow component (As), or both. We studied Na channel recovery at ‐150 mV from inactivation using whole cell voltage clamp of rat ventricular cells at 23°C using a two‐pulse recovery protocol. Longer conditioning durations dramatically increased As, (from 12% for tc= 500 msec to 37% for tc= 4(MM) msec, P < 0.01). Neither τt (6 vs 5 msec) nor τs, (115 vs 140 msec) were significantly affected. In a second set of experiments, the recovery potential was depolarized to a potential at which the sodium current was 70% available (≅‐105 mV). This recovery potential had no significant effect on As, but both τf and τs were significantly slower (e.g., at tc= 2s, τs= 147 msec and As, = 28% at Vr= ‐150 mV, and τs, = 456 msec and As, = 29% at Vr, ≅ ‐105 mV). In addition, a 1‐ to 2‐msec lag in the onset of recovery was prominent at the depolarized recovery potentials. Conclusions: Our results support a model for slow recovery where conditioning duration determines entry into an inactivated state from which Na channels recover slowly, and recovery potential determines the rate of recovery from this state. A kinetic scheme with at least three inactivated states is proposed. These results also have implications for cardiac excitability under conditions, such as ischemia, where membranes are depolarized.

AB - Slow Recovery of INa. introduction: Recovery of the Na channel from inactivation is essential to the normal conduction and refractoriness of the myocardium. In addition to fast recovery, occurring within several milliseconds at hyperpolarized potentials, a component of the current exhibits slow recovery occurring over hundreds of milliseconds. Long conditioning depolarizations potentiate slow recovery. Methods and Results: This study was designed to test conditioning durations (tc) between 0.25 and 4 seconds (s) as to whether recovery was slowed by an effect on the fast (τt) and slow (τs) time constants of recovery, the relative amplitude of the slow component (As), or both. We studied Na channel recovery at ‐150 mV from inactivation using whole cell voltage clamp of rat ventricular cells at 23°C using a two‐pulse recovery protocol. Longer conditioning durations dramatically increased As, (from 12% for tc= 500 msec to 37% for tc= 4(MM) msec, P < 0.01). Neither τt (6 vs 5 msec) nor τs, (115 vs 140 msec) were significantly affected. In a second set of experiments, the recovery potential was depolarized to a potential at which the sodium current was 70% available (≅‐105 mV). This recovery potential had no significant effect on As, but both τf and τs were significantly slower (e.g., at tc= 2s, τs= 147 msec and As, = 28% at Vr= ‐150 mV, and τs, = 456 msec and As, = 29% at Vr, ≅ ‐105 mV). In addition, a 1‐ to 2‐msec lag in the onset of recovery was prominent at the depolarized recovery potentials. Conclusions: Our results support a model for slow recovery where conditioning duration determines entry into an inactivated state from which Na channels recover slowly, and recovery potential determines the rate of recovery from this state. A kinetic scheme with at least three inactivated states is proposed. These results also have implications for cardiac excitability under conditions, such as ischemia, where membranes are depolarized.

UR - http://www.scopus.com/inward/record.url?scp=0028841871&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028841871&partnerID=8YFLogxK

U2 - 10.1111/j.1540-8167.1995.tb00355.x

DO - 10.1111/j.1540-8167.1995.tb00355.x

M3 - Article

C2 - 8542075

AN - SCOPUS:0028841871

VL - 6

SP - 786

EP - 795

JO - Journal of Cardiovascular Electrophysiology

JF - Journal of Cardiovascular Electrophysiology

SN - 1045-3873

IS - 10

ER -