Zinc-induced changes in ionic currents of cardiomyocytes

Area of Science:

• Cardiology
• Cell Physiology
• Trace Element Research

Background:

• Zinc plays a role in cellular functions, but its specific effects on cardiac ion channels are not fully understood.
• Pathological conditions can alter zinc levels within cardiomyocytes, potentially affecting cardiac function.

Purpose of the Study:

• To investigate the impact of extracellular and intracellular zinc on L-type Ca2+ channel currents (ICa) in isolated ventricular myocytes.
• To differentiate the effects of zinc based on its location (extracellular vs. intracellular) and concentration.

Main Methods:

• Whole-cell voltage-clamp technique applied to isolated ventricular myocytes.
• Application of extracellular zinc chloride (ZnCl2) and intracellular zinc elevation using Zn-pyrithione.
• Use of N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) to chelate intracellular zinc.

Main Results:

• Extracellular zinc (micromolar) reversibly reduced ICa by 30% without altering the current-voltage relationship.
• Increased intracellular free zinc ([Zn2+]i) inhibited peak ICa by 33% and shifted the voltage dependency.
• TPEN strongly inhibited ICa (42%), suggesting a role for endogenous intracellular zinc.

Conclusions:

• Both extracellular and intracellular zinc alterations can modify cardiac ICa, but through distinct mechanisms.
• These findings highlight potential cardiovascular side effects of altered zinc levels in pathological states.
• Consideration of zinc's dual role is crucial for cardiovascular cell integrity and function.