Magnesium and Cardiac Action Potential

Magnesium (Mg++) is the second most abundant intracellular ion.

Normal Serum Mg++ is 1.8 to 2.5 mg/dL or .8 to 1.5 mmol/L (millimoles per liter)

(This values may vary depending on sources)

Keep in mind, the Mg++ concentration in the average adult is approximately 25g, but most of our Mg++ is found in bones and intracellular. Because this makes it hard to assess the true Mg++ concentration, true Mg++ measurement is often not performed, instead, Serum Mg++ levels are obtained. This measurement does not fully correlate with overall Mg++ because only a small amount is found in the serum, usually approximately 1% of all Mg++.

Mg++ has over 300 different physiologic functions, and it affects multiple phases of the cardiac AP.

  • Mg++ acts as a physiologic Calcium (Ca++) Channel inhibitor by slowing slow L-Type Calcium channel during PHASE 2 of the AP
  • This reduces further Ca++ release by the Sarcoplasmic Reticulum which leads to reduced automaticity, contractility and conductivity through cardiac tissue, including the AVN

Hypomagnesemia (Serum Mg++ < 1.8 mg/dL or .8 mmol/L)

  • Mg++ mediates Potassium (K+) influx during PHASE 4 of the AP, therefore, during Hypomagnesemia, K+ influx is partially inhibited, which leads to delayed ventricular repolarization.
  • Because Mg++ also is responsible for proper Na+/K+ pump, Hypomagnesemia leads to K+ loss which leads to Hypokalemia (serum K+ < 3 mEql/L).

Whang et al studied 46 Hypokalemic patients who also presented with Hypomagnesemia. In these cases, the Hypokalemia was only corrected when the associated Hypomagnesemia was fixed.

“Review Clinical disorders of magnesium metabolism.
Whang R
Compr Ther. 1997 Mar; 23(3):168-73.”

Common Hypomagnesemia causes include:

– Alcoholism

– Diabetic Ketoacidosis

– Malnutrition

– Digoxin

– Diuretics (e.g. Thiazides, Loop Diuretics)

ECG Changes consistent with Hypomagnesemia:-

  • ST segment depression (horizontal or downsloping ST segment)
  • Tachycardia leading to bradycardia
  • Diminished T wave amplitude or flattened T waves
  • Presence of U waves (associated with Hypokalemia)
  • Widened QRS complex >100ms (rare)
  • Prolonged QTc (due to repolarization delay)
  • Prolonged PR interval
  • Torsade De Pointes (Polymorphic Ventricular Tachycardia)


– ST depression in V3-6 and Leads II and III

– Diminished T waves

– Serum Magnesium = 1.5 mg/dL

– Serum K+ = 3.7 mEq/L



– Flattened T waves

– Prolonged QT appearance due to prominent U wave

– Serum K+ = < 2 mEq/L


– Torsade De Pointes


Although not every Hypomagnesemia case will present with ECG changes, these changes may be seen often and have similar Hypokalemic characteristics, as Magnesium plays a role in Potassium regulation.


  • Charlene says:

    Thank you for this information. Just yesterday I was asking my instructor about the MOA of Mg in Torsades and how it affects QTc . I didn’t exactly receive the most satisfactory answer. This makes it very clear.

    • Ivan Rios says:

      You’re welcome. I wish medic school went a little more in depth when it comes to pharmacodynamics and such. I’m glad this helped!

  • Jonathan says:

    I have a background in biochemistry, and so am able to navigate the medical science more than someone without this background. My mom has atrial fibrillation, and so I decided to do some investigation. I am AMAZED to find out how little her primary care doctor knows about Magnesium/Potassium/Calcium concentrations as they pertain to Atrial fibrillation. On top of all of that, she has been on Thiazide diuretics for years, despite the atrial fibrillation. Thiazide diuretics can certainly alter concentrations of electrolytes such as potassium, calcium, and magnesium. It is listed in this article that this can lead to hypomagnesemia (low Magnesium). It can also lead to hypokalemia (low potassium), and hypercalcemia (high calcium). I will meet with the cardiologist next week and discuss all of this. How many times does “standard medical care” lead to very undesirable side effects, simply because non profitable “drugs” such as minerals are not taught in medical school.

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