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Assessment of Sarcoplasmic Reticulum Calcium Reserve and Intracellular Diastolic Calcium Removal in Isolated Ventricular Cardiomyocytes
11:00

Assessment of Sarcoplasmic Reticulum Calcium Reserve and Intracellular Diastolic Calcium Removal in Isolated Ventricular Cardiomyocytes

Published on: September 18, 2017

Late sodium current contributes to diastolic cell Ca2+ accumulation in chronic heart failure

Nidas A Undrovinas1, Victor A Maltsev, Luiz Belardinelli

  • 1Department of Internal Medicine, Henry Ford Hospital, Detroit, MI 48202-2689, USA.

The Journal of Physiological Sciences : JPS
|May 22, 2010
PubMed

Insights

Late sodium current (INaL) contributes to diastolic calcium (DCa) buildup and spontaneous calcium release in heart failure (HF). Blocking INaL improves function in failing heart cells, offering a potential therapeutic target.

Area of Science:

  • Cardiovascular Physiology
  • Cardiac Electrophysiology
  • Heart Failure Pathophysiology

Background:

  • Chronic heart failure (HF) is associated with altered intracellular calcium handling.
  • The role of late sodium current (INaL) in diastolic calcium (DCa) accumulation in HF remains incompletely understood.

Purpose of the Study:

  • To elucidate the contribution of INaL to DCa accumulation and spontaneous Ca2+ release in a canine model of chronic heart failure.
  • To investigate the therapeutic potential of INaL blockade in improving cardiac function in HF.

Main Methods:

  • HF was induced in dogs via coronary microembolizations.
  • Ventricular myocytes (VM) were isolated and loaded with fluo-4 for Ca2+ transient recordings.
  • Patch-clamp techniques were used to record INaL and action potentials.
  • In silico modeling of excitation-contraction coupling was employed to validate findings.

Main Results:

  • Failing VMs exhibited prolonged action potentials and Ca2+ transients at low pacing rates.
  • Significant DCa accumulation and spontaneous Ca2+ releases were observed in failing VMs at higher pacing rates.
  • Selective INaL blockade with ranolazine or tetrodotoxin reversibly improved function in failing VMs.
  • In silico models confirmed the role of INaL in DCa accumulation and the efficacy of INaL blockade.

Conclusions:

  • INaL plays a significant role in diastolic Ca2+ accumulation in chronic heart failure.
  • INaL contributes to arrhythmogenic spontaneous Ca2+ release in failing hearts.
  • Targeting INaL represents a promising therapeutic strategy for managing heart failure.

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