scholarly journals Inhibition of Small Conductance Calcium-Activated Potassium (SK) Channels Prevents Arrhythmias in Rat Atria During β-Adrenergic and Muscarinic Receptor Activation

2018 ◽  
Vol 9 ◽  
Author(s):  
Lasse Skibsbye ◽  
Anne K. Bengaard ◽  
A. M. Uldum-Nielsen ◽  
Kim Boddum ◽  
Torsten Christ ◽  
...  
Keyword(s):  
Muscarinic Receptor ◽  
Receptor Activation ◽  
Sk Channels ◽  
Rat Atria ◽  
Small Conductance

scholarly journals Dendritic small conductance calcium-activated potassium channels activated by action potentials suppress EPSPs and gate spike-timing dependent synaptic plasticity

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Scott L Jones ◽  
Minh-Son To ◽  
Greg J Stuart
Keyword(s):  
Synaptic Plasticity ◽  
Potassium Channels ◽  
Action Potentials ◽  
Pyramidal Neurons ◽  
Receptor Activation ◽  
Spike Timing ◽  
Sk Channels ◽  
Sk Channel ◽  
Calcium Activated Potassium Channels ◽  
Small Conductance

Small conductance calcium-activated potassium channels (SK channels) are present in spines and can be activated by backpropagating action potentials (APs). This suggests they may play a critical role in spike-timing dependent synaptic plasticity (STDP). Consistent with this idea, EPSPs in both cortical and hippocampal pyramidal neurons were suppressed by preceding APs in an SK-dependent manner. In cortical pyramidal neurons EPSP suppression by preceding APs depended on their precise timing as well as the distance of activated synapses from the soma, was dendritic in origin, and involved SK-dependent suppression of NMDA receptor activation. As a result SK channel activation by backpropagating APs gated STDP induction during low-frequency AP-EPSP pairing, with both LTP and LTD absent under control conditions but present after SK channel block. These findings indicate that activation of SK channels in spines by backpropagating APs plays a key role in regulating both EPSP amplitude and STDP induction.

scholarly journals Cardiac small-conductance calcium-activated potassium channels in health and disease

2021 ◽  
Vol 473 (3) ◽  
pp. 477-489 ◽  
Author(s):  
Xiao-Dong Zhang ◽  
Phung N. Thai ◽  
Deborah K. Lieu ◽  
Nipavan Chiamvimonvat
Keyword(s):  
Ventricular Myocytes ◽  
Pulmonary Veins ◽  
Differential Sensitivity ◽  
Sk Channels ◽  
Sk Channel ◽  
Ventricular Cells ◽  
Intracellular Ca ◽  
Life Threatening ◽  
Health And Disease ◽  
Small Conductance

AbstractSmall-conductance Ca2+-activated K+ (SK, KCa2) channels are encoded by KCNN genes, including KCNN1, 2, and 3. The channels play critical roles in the regulation of cardiac excitability and are gated solely by beat-to-beat changes in intracellular Ca2+. The family of SK channels consists of three members with differential sensitivity to apamin. All three isoforms are expressed in human hearts. Studies over the past two decades have provided evidence to substantiate the pivotal roles of SK channels, not only in healthy heart but also with diseases including atrial fibrillation (AF), ventricular arrhythmia, and heart failure (HF). SK channels are prominently expressed in atrial myocytes and pacemaking cells, compared to ventricular cells. However, the channels are significantly upregulated in ventricular myocytes in HF and pulmonary veins in AF models. Interests in cardiac SK channels are further fueled by recent studies suggesting the possible roles of SK channels in human AF. Therefore, SK channel may represent a novel therapeutic target for atrial arrhythmias. Furthermore, SK channel function is significantly altered by human calmodulin (CaM) mutations, linked to life-threatening arrhythmia syndromes. The current review will summarize recent progress in our understanding of cardiac SK channels and the roles of SK channels in the heart in health and disease.

scholarly journals Bedside to Bench: Role of Muscarinic Receptor Activation in Ultrarapid Growth of Colorectal Cancer in a Patient With Pheochromocytoma

2013 ◽  
Vol 88 (11) ◽  
pp. 1340-1346 ◽  
Author(s):  
Erik C. von Rosenvinge ◽  
Kunrong Cheng ◽  
Cinthia B. Drachenberg ◽  
Carol B. Fowler ◽  
David L. Evers ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Muscarinic Receptor ◽  
Receptor Activation

Muscarinic receptor activation disrupts hippocampal sharp wave-ripples

2012 ◽  
Vol 1461 ◽  
pp. 1-9 ◽  
Author(s):  
Hiroaki Norimoto ◽  
Mika Mizunuma ◽  
Daisuke Ishikawa ◽  
Norio Matsuki ◽  
Yuji Ikegaya
Keyword(s):  
Muscarinic Receptor ◽  
Receptor Activation ◽  
Sharp Wave

scholarly journals Acetylcholine-induced neuronal differentiation: muscarinic receptor activation regulates EGR-1 and REST expression in neuroblastoma cells

2009 ◽  
Vol 108 (3) ◽  
pp. 821-834 ◽  
Author(s):  
Monica Salani ◽  
Tonino Anelli ◽  
Gabriella Augusti Tocco ◽  
Elena Lucarini ◽  
Chiara Mozzetta ◽  
...  
Keyword(s):  
Neuronal Differentiation ◽  
Muscarinic Receptor ◽  
Neuroblastoma Cells ◽  
Receptor Activation

Abstract 17319: Distinct Effects of Human Calmodulinopathy on the Function of Small Conductance Ca 2+ -Activated K + (SK) Channels

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
Hannah A Ledford ◽  
Seojin Park ◽  
Duncan Muir ◽  
Wen Smith ◽  
Ryan L Woltz ◽  
...  
Keyword(s):  
Ion Channels ◽  
Intracellular Signaling ◽  
Critical Role ◽  
Dominant Negative ◽  
Polymorphic Ventricular Tachycardia ◽  
Dominant Negative Effect ◽  
Sk Channels ◽  
Channel Function ◽  
Sk Channel ◽  
Small Conductance

Background: Calmodulin (CaM) plays a critical role in intracellular signaling and regulation of Ca 2+ -dependent ion channels. Mutations in CALM1, CALM2, and CALM3 have recently been linked to cardiac arrhythmias, such as Long QT Syndrome (LQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT), and familial idiopathic ventricular fibrillation (IVF). Small-conductance Ca 2+ - activated K + channels (SK) are voltage-independent channels that are regulated solely from beat-to-beat changes in intracellular calcium. CaM regulates the function of multiple ion channels, including SK channels, although the effect of CaM mutations on these channels is not yet understood. We hypothesize that human CaM mutations linked to sudden cardiac death disrupt SK channel function by distinct mechanisms. Methods and Results: We tested the effects of LQTS (CaM D96V , CaM D130G ), CPVT (CaM N54I , CaM N98S ), and IVF (CaM F90L ) CaM mutants compared to CaM WT on SK channel function. Using whole-cell voltage-clamp recordings, we found that CaM D96V and CaM D130G mutants significantly inhibited apamin-sensitive currents. Similarly, action potential studies in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) also revealed significant knockdown of apamin-sensitive currents. Immunofluorescent confocal microscopy confirmed that this effect was not due to changes in SK channel trafficking. Rather, co-immunoprecipitation studies showed a significant decrease in the association of these CaM mutants with the SK channel. Rosetta molecular modeling was used to identify a conformational change in CaM F90L structure compared to that of CaM WT . Conclusions: We found that CaM D96V and CaM D130G mutants significantly reduced apamin-sensitive currents, through a dominant negative effect on SK channel function. Consistent with our hypothesis, CaM F90L resulted in the least inhibitory effects. The data suggests that specific mutations with phenylalanine to leucine (CaM F90L ) may disrupt the interaction between apo-CaM with CaMBD on the SK2 channel.

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