Cardiac transient outward potassium current

The cardiac transient outward potassium current (referred to as I_to1 or I_to^[1]) is one of the ion currents across the cell membrane of heart muscle cells. It is responsible for the (brief) repolarizing phase 1 of the cardiac action potential (which suceeds depolarisation, and precedes the plateau phase).^[2] The I_to is produced by movement of positively charged potassium (K⁺) ions from the intracellular into the extracellular space. It exhibits rapid activation and inactivation.^[3] I_to1 is complemented with I_to2 resulting from Cl⁻ ions to form the transient outward current I_to.^{[citation needed]}

The cardiac action potential has five phases. I_to1 is active during phase 1, causing a fast repolarization of the action potential

The I_to1 is generated by voltage-gated K+ channels Kv1.4, Kv4.2, and (especially) Kv4.3; these channels undergo ball-and-chain inactivation to terminate the current.^[3]

It occurs in atrial, ventricular, and conduction system cells. In ventricular myocardium, it is more potent in the epicardium than the endocardium; this transmural I_to1 gradient underlies the J wave ECG finding.^[3]

Role in disease

• Reduction in I_to1 density is associated with prolonged action potentials and is a common finding in cardiac disease.^[4]

• I_to1 density is significantly lower in the cells of a failing heart in comparison to the cells of a healthy heart.^[5]
• There is correlation between decreased I_to1 density and atrial fibrillation.^[6]
• I_to activation is inhibited by thyrotropin (TSH).^[7] This mechanisms may be one of the reasons for the observation that both bradycardia and atrial fibrillation are common in hypothyroidism.^[8][9][10]

• An increase in the I_to1 density caused by a mutation in Kv4.3 can be a cause of Brugada Syndrome.^[11]