Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.17 (CaMKII)
 4,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The large conductance, calcium-sensitive K+ channel (BKCa channel) is a voltage-activated ion channel in which direct calcium binding shifts gating to more negative cellular membrane potentials. We hypothesized that the calcium-binding domain of BKCa channels may mimic the role played by calmodulin (CaM) in the activation of calcium-CaM-dependent enzymes, in which a tonic inhibitory constraint is removed on CaM binding. To examine such a hypothesis, we used peptides from the autoregulatory domains of CaM kinase II (CK291-317) and cNOS (the constitutive nitric oxide synthase; cNOS725-747) as probes for the calcium-dependent activation of murine BKCa channels transiently expressed in HEK 293 cells. We found that these CaM-binding peptides produced potent, time-dependent inhibition of mammalian BKCa channel current following voltage-dependent activation. Inhibition was observed in both the presence and the absence of cytosolic free calcium. Similar application of CK291-31 had no effect on either the amplitude or kinetics of voltage-dependent, macroscopic currents recorded from rabbit smooth muscle Kv1.5 potassium channels transiently expressed in HEK 293 cells. Cytosolic application of both CK291-317 and tetraethylammonium (TEA) produced an additive and non-competitive block of BKCa current. This finding suggests that the peptide-binding site is distinct (e.g. outside the pore region of the channel) from that of TEA. Our results are thus consistent with a model in which the BKCa channel's voltage-dependent gating process is under an intramolecular constraint that is relieved upon calcium binding. The intrinsic calcium sensor of the channel may thus interact with an inhibitory domain present in the BKCa channel, and by doing so, remove an inhibitory 'constraint' that permits voltage-dependent gating to occur at more negative potentials.
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PMID:Inhibition of a mammalian large conductance, calcium-sensitive K+ channel by calmodulin-binding peptides. 1099 May 35

Colchicine is a microtubule disruptor that reduces the occurrence of atrial fibrillation (AF) after an operation or ablation. However, knowledge of the effects of colchicine on atrial myocytes is limited. The aim of this study was to determine if colchicine can regulate calcium (Ca(2+) ) homeostasis and attenuate the electrical effects of the extracellular matrix on atrial myocytes. Whole-cell clamp, confocal microscopy with fluorescence, and western blotting were used to evaluate the action potential and ionic currents of HL-1 cells treated with and without (control) colchicine (3 nM) for 24 hrs. Compared with control cells, colchicine-treated HL-1 cells had a longer action potential duration with smaller intracellular Ca(2+) transients and sarcoplasmic reticulum (SR) Ca(2+) content by 10% and 47%, respectively. Colchicine-treated HL-1 cells showed a smaller L-type Ca(2+) current, reverse mode sodium-calcium exchanger (NCX) current and transient outward potassium current than control cells, but had a similar ultra-rapid activating outward potassium current and apamin-sensitive small-conductance Ca(2+) -activated potassium current compared with control cells. Colchicine-treated HL-1 cells expressed less SERCA2a, total, Thr17-phosphorylated phospholamban, Cav1.2, CaMKII, NCX, Kv1.4 and Kv1.5, but they expressed similar levels of the ryanodine receptor, Ser16-phosphorylated phospholamban and Kv4.2. Colchicine attenuated the shortening of the collagen-induced action potential duration in HL-1 cells. These findings suggest that colchicine modulates the atrial electrical activity and Ca(2+) regulation and attenuates the electrical effects of collagen, which may contribute to its anti-AF activity.
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PMID:Colchicine modulates calcium homeostasis and electrical property of HL-1 cells. 2692 94