SK Channels and Heart Disease

Abstract

Extensive evidence indicates that small-conductance Ca2+-activated K+ channels (SK channels) help regulate cardiac rhythm and myocardial function in physiological and pathophysiological conditions. This chapter will begin by discussing the basic physiology of SK channel expression, localization, and activation under normal conditions, before proceeding to address the impact of SK channel dysfunction on a variety of cardiac pathologies including atrial fibrillation (AF), ventricular arrhythmias (VA), cardiac hypertrophy/heart failure (HF) and myocardial ischemia/reperfusion (IR) injury. The critical role of aberrant SK channel regulation will also be discussed to establish unifying mechanisms of SK channel pathology across these different conditions. Several animal model and human tissue experiments suggest that pharmacologic modulation of SK channel function may be beneficial in controlling AF, VA, cardiomyopathy and myocardial IR injury. Therefore, targeting SK channels may represent a promising new therapeutic avenue for treating a variety of cardiovascular disease states.

Challenges in the Therapeutic Targeting of KCa Channels: From Basic Physiology to Clinical Applications

“…In one study, SK2 mRNA expression in the atrial tissue of patients with AF was lower than that in the healthy group [ 200 ]. Inconsistencies in the levels of SK channel mRNA and protein may be due to the stage or duration of AF, the pathogenesis model, and differences in atrial tissue among species [ 193 , 201 ]. SK channels might be initially upregulated and then downregulated due to extensive structural and electrical remodeling in the atrium [ 193 , 201 ].…”

“…Inconsistencies in the levels of SK channel mRNA and protein may be due to the stage or duration of AF, the pathogenesis model, and differences in atrial tissue among species [ 193 , 201 ]. SK channels might be initially upregulated and then downregulated due to extensive structural and electrical remodeling in the atrium [ 193 , 201 ]. Therefore, SK channel antagonists might be potential candidates for the treatment of AF onset before SK channel expression is downregulated [ 193 ].…”

Presence of Small-Conductance Calcium-Activated Potassium (SK) Channels in the Central and Peripheral Nervous Systems and Their Role in Health and Disease

“…Overall, SK channels are classified into three isoforms: SK1, SK2, and SK3, based on their gene origin and their sensitivity to the bee venom, apamin [21,22]. An overall view of these subtypes is presented in Table 1 (Ref.…”

“…The SK1 channel is moderately sensitive to apamin, and its gene is located on chromosome 19, whereas the SK2 channel has the strongest affinity for apamin and is located on chromosome 5. SK3 is moderately sensitive to apamin, and its gene is located on chromosome 1 [21]. The third column refers to other commonly used nomenclatures.…”