Small-conductance Ca2+-activated K+ channels promote J-wave syndrome and phase 2 reentry

Landaw, Julian; Zhang, Zhaoyang; Song, Zhen; Liu, Michael B.; Olcese, Riccardo; Chen, Peng Sheng; Weiss, James N.; Qu, Zhilin

doi:10.1016/j.hrthm.2020.04.023

Cited by 10 publications

(11 citation statements)

References 34 publications

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“…SK channel blockade in this rabbit model was antiarrhythmic-JWS was reduced and SVF was abolished, suggesting that SK current activation contributed to the development JWS and SVF in rabbit ventricles [109]. A recent study showed that colocalization of LTCC and SK channels in ventricular myocytes activates SK currents, which then promote phase 2 reentry and T-wave alternans, leading to JWS and VA [115].…”

Section: Sk Channels In Ventricular Arrhythmias and Heart Failurementioning

confidence: 64%

SK Channels and Heart Disease

Zhong¹,

Kant²,

Sellke³

et al. 2022

Ion Transporters - From Basic Properties to Medical Treatment

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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.

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Section: Sk Channels In Ventricular Arrhythmias and Heart Failurementioning

confidence: 64%

SK Channels and Heart Disease

Zhong¹,

Kant²,

Sellke³

et al. 2022

Ion Transporters - From Basic Properties to Medical Treatment

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“…In addition to inward rectification of SK channels, the modulation of SK channel sensitivity to activation by Ca 2þ is another important factor that may alter SK channel kinetics and its contribution to AP repolarization, as shown in a modeling study (67). Experimental results have shown that protein kinase CK2 interacts with SK channels and phosphorylates SK-bound calmodulin to reduce the Ca 2þ sensitivity of SK channels (68,69).…”

Section: Discussionmentioning

confidence: 96%

Impact of ISK Voltage and Ca2+/Mg2+-Dependent Rectification on Cardiac Repolarization

Bronk

Kim

Polina

et al. 2020

Biophysical Journal

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Cardiac small conductance Ca 2þ -activated K þ (SK) channels are activated solely by Ca 2þ , but the SK current (I SK ) is inwardly rectified. However, the impact of inward rectification in shaping action potentials (APs) in ventricular cardiomyocytes under b-adrenergic stimulation or in disease states remains undefined. Two processes underlie this inward rectification: an intrinsic rectification caused by an electrostatic energy barrier from positively charged amino acids at the inner pore and a voltage-dependent Ca 2þ /Mg 2þ block. Thus, Ca 2þ has a biphasic effect on I SK , activating at low [Ca 2þ ] yet inhibiting I SK at high [Ca 2þ ]. We examined the effect of I SK rectification on APs in rat cardiomyocytes by simultaneously recording whole-cell apamin-sensitive currents and Ca 2þ transients during an AP waveform and developed a computer model of SK channels with rectification features. The typical profile of I SK during AP clamp included an initial peak (mean 1.6 pA/pF) followed by decay to the point that submembrane [Ca 2þ ] reached $10 mM. During the rest of the AP stimulus, I SK either plateaued or gradually increased as the cell repolarized and submembrane [Ca 2þ ] decreased further. We used a six-state gating model combined with intrinsic and Ca 2þ /Mg 2þ -dependent rectification to simulate I SK and investigated the relative contributions of each type of rectification to AP shape. This SK channel model replicates key features of I SK recording during AP clamp showing that intrinsic rectification limits I SK at high V m during the early and plateau phase of APs. Furthermore, the initial rise of Ca 2þ transients activates, but higher [Ca 2þ ] blocks SK channels, yielding a transient outward-like I SK trajectory. During the decay phase of Ca 2þ , the Ca 2þ -dependent block is released, causing I SK to rise again and contribute to repolarization. Therefore, I SK is an important repolarizing current, and the rectification characteristics of an SK channel determine its impact on early, plateau, and repolarization phases of APs.

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“…Como base para este estudio se tomó el modelo de O'Hara et al [4], modificado según [5] para representar condiciones de IC. Posteriormente se incluyó la formulación propuesta en [6] para la corriente I SK . Los parámetros de la ecuación de I SK se fijaron en concordancia con observaciones experimentales [6,7]:…”

Section: Métodosunclassified

“…Posteriormente se incluyó la formulación propuesta en [6] para la corriente I SK . Los parámetros de la ecuación de I SK se fijaron en concordancia con observaciones experimentales [6,7]:…”

Section: Métodosunclassified