Coupling of SK channels, L-type Ca2+ channels, and ryanodine receptors in cardiomyocytes

Abstract

Small-conductance Ca2+-activated K+ (SK) channels regulate the excitability of cardiomyocytes by integrating intracellular Ca2+ and membrane potentials on a beat-to-beat basis. The inextricable interplay between activation of SK channels and Ca2+ dynamics suggests the pathology of one begets another. Yet, the exact mechanistic underpinning for the activation of cardiac SK channels remains unaddressed. Here, we investigated the intracellular Ca2+ microdomains necessary for SK channel activation. SK currents coupled with Ca2+ influx via L-type Ca2+ channels (LTCCs) continued to be elicited after application of caffeine, ryanodine or thapsigargin to deplete SR Ca2+ store, suggesting that LTCCs provide the immediate Ca2+ microdomain for the activation of SK channels in cardiomyocytes. Super-resolution imaging of SK2, Cav1.2 Ca2+ channel, and ryanodine receptor 2 (RyR2) was performed to quantify the nearest neighbor distances (NND) and localized the three molecules within hundreds of nanometers. The distribution of NND between SK2 and RyR2 as well as SK2 and Cav1.2 was bimodal, suggesting a spatial relationship between the channels. The activation mechanism revealed by our study paved the way for the understanding of the roles of SK channels on the feedback mechanism to regulate the activities of LTCCs and RyR2 to influence local and global Ca2+ signaling.

Sex‐specific activation of SK current by isoproterenol facilitates action potential triangulation and arrhythmogenesis in rabbit ventricles

“…Since I KAS is very sensitive to local Ca 2+ between the SK channel and LTCC/RyR (Zhang et al . ), it is possible that I KAS recorded at a fixed global Ca 2+ concentration was not high enough to differentially activate I KAS between sexes. Further studies with dynamical Ca 2+ fluctuations are needed.…”

Spin transport parameters of NbN thin films characterized by spin pumping experiments

“…This value quantified by the Hanle model can be compared with independently calculated from the spin diffusion model as already discussed above, i.e. = ( ) 2 / where D is the Einstein diffusion coefficient (its value equal to 0.4−0.56 cm 2 /s was taken from Ref [40]…”

Modulation of SK Channels: Insight Into Therapeutics of Atrial Fibrillation

“…Moreover, the expression of L-type Ca 21 channels plays a significant role in functions of SK2 channels in atrial myocytes. Zhang et al [25] observed the close distribution of SK2, Ca v 1.2 Ca 21 channels and ryanodine receptor type 2 in cardiomyocytes, indicating a spatial relationship between these channels. Three (3) molecules were localised within hundreds of nanometers.…”