Transient outward potassium channel regulation in healthy and diabetic hearts.
Diabetic patients have a higher incidence of cardiac arrhythmias, including ventricular fibrillation and sudden death, and show important alterations in the electrocardiogram, most of these related to the repolarization. In myocytes isolated from diabetic hearts, the transient outward K+ current (Ito) is the repolarizing current that is mainly affected. Type 1 diabetes alters Ito at 3 levels: the recovery of inactivation, the responsiveness to physiologic regulators, and the functional expression of the channel. Diabetes slows down Ito recovery of inactivation because it triggers the switching from fast-recovering Kv4.x channels to the slow-recovering Kv1.4. Diabetic animals also have decreased responsiveness of Ito towards the sympathetic nervous system; thus, the diabetic heart develops a resistance to its physiologic regulator. Finally, diabetes impairs support of various trophic factors required for the functional expression of the channel and reduces Ito amplitude by decreasing the amount of Kv4.2 and Kv4.3 proteins.
Gallego
Mónica
M
Department of Physiology, School of Pharmacy, Universidad del País Vasco, P.O. Box 699, Bilbao 48080, Spain.
Alday
Aintzane
A
Urrutia
Janire
J
Casis
Oscar
O
D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism* / Q000503:physiopathology; D048909:Diabetes Complications / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007700:Kinetics; D051665:Kv1.4 Potassium Channel / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*; D051672:Shal Potassium Channels / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000503:physiopathology
D051665:Kv1.4 Potassium Channel; D015221:Potassium Channels; D051672:Shal Potassium Channels