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Cardiovascular Physiology Concepts

Richard E. Klabunde, PhD


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Ion Channels


The cell membrane is permeable to several ions, the most important of which are Na+, K+, Ca++ and Cl-. These ions pass across the membrane through specific ion channels that can open (become activated) and close (become inactivated). Therefore, these channels are said to be gated channels. Their opening and closing can occur in response to

  1. voltage changes (voltage gated channels)
  2. ligand activation of receptors (receptor gated channels)
  3. specific ions and chemical ligands

Cardiac cells can have multiple channels for a particular ion. For example, there are many different types of potassium channels that play an important role in resting membrane potential and in action potentials. It is the opening and closing of ion channels that alters specific ion conductances in a manner that determines resting potentials and generates action potentials. For example, when an action potential is elicited in a cardiomyocyte, sodium channels transiently open and potassium channels close, which leads to depolarization. Shortly thereafter (within a few milliseconds), the sodium channels close and calcium channels open to maintain a depolarized state. This is followed by inactivation of the calcium channels and a reopening of the potassium channels, which leads to membrane repolarization.

The following table summarizes some of the important ion channels that are found in cardiac and vascular smooth muscle cells:

Sodium Channels  
Fast Na+ Phase 0 depolarization of non-pacemaker cardiac action potentials
Slow Na+ "Funny" pacemaker current (If) in cardiac nodal tissue
Potassium Channels  
Inward rectifier
(Iir or IK1)
Contributes to late phase 3 repolarization; maintains phase 4 negative potential 
Transient outward (Ito) Contributes to phase 1 of non-pacemaker cardiac action potentials
Delayed rectifiers
(IKr and IKs)
Rapid and slow delayed K+ channels; phase 3 repolarization of cardiac action potentials
KATP channels that are inhibited by ATP; therefore, open when ATP decreases during hypoxia. In vascular smooth muscle, adenosine removes the ATP inhibition and opens these channels, producing hyperpolarization and vasodilation.
Acetylcholine-activated (IK, ACh) Activated by acetylcholine; Gi-protein coupled
Calcium-activated (IK, Ca or BKCa) Open in response to Ca++ influx in vascular smooth muscle
Calcium Channels  
L-type (ICa-L) Slow inward, long-lasting current; phase 2 non-pacemaker cardiac action potentials and late phase 4 and phase 0 of SA and AV nodal cells; important in vascular smooth muscle contraction
T-type (ICa-T) Transient current that contributes to early phase 4 pacemaker currents in SA and AV nodal cells

Many of the antiarrhythmic drugs that are used to treat cardiac arrhythmias have their action on sodium, calcium and potassium channels.

Revised 12/1/2022


DISCLAIMER: These materials are for educational purposes only, and are not a source of medical decision-making advice.