A5004430534- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Neuroscience and Neuropharmacology Research
- Nicotinic Acetylcholine Receptors Study
- Lipid Membrane Structure and Behavior
- Neuroscience and Neural Engineering
- Cardiovascular Effects of Exercise
- Trace Elements in Health
- Neuroendocrine regulation and behavior
- Cardiomyopathy and Myosin Studies
- Nanopore and Nanochannel Transport Studies
- Hypothalamic control of reproductive hormones
- Photoreceptor and optogenetics research
- Receptor Mechanisms and Signaling
- Ion Channels and Receptors
- Signaling Pathways in Disease
- Electrochemical Analysis and Applications
- Mitochondrial Function and Pathology
- Fibroblast Growth Factor Research
- Fuel Cells and Related Materials
- Protein Kinase Regulation and GTPase Signaling
- Stress Responses and Cortisol
- Neurogenesis and neuroplasticity mechanisms
- Iron Metabolism and Disorders
- Analytical Chemistry and Sensors
Slovak Academy of Sciences
2013-2024
Centre of Biosciences of the Slovak Academy of Sciences
2017-2024
Columbia University
2001
Comenius University Bratislava
1997-1998
Excitation-contraction coupling in heart muscle requires the activation of Ca(2+)-release channels/type 2 ryanodine receptors (RyR2s) by Ca(2+) influx. RyR2s are arranged on sarcoplasmic reticular membrane closely packed arrays such that their large cytoplasmic domains contact one another. We now show multiple can be isolated under conditions they remain physically coupled to When these channels examined planar lipid bilayers, exhibit simultaneous gating, termed "coupled gating." Removal...
Ryanodine receptors (RyRs), intracellular calcium release channels required for cardiac and skeletal muscle contraction, are macromolecular complexes that include kinases phosphatases. Phosphorylation/dephosphorylation plays a key role in regulating the function of many ion channels, including RyRs. However, mechanism by which phosphatases targeted to is not well understood. We have identified novel involved formation channel complexes: kinase phosphatase targeting proteins binding via...
The type 1 ryanodine receptor (RyR1) on the sarcoplasmic reticulum (SR) is major calcium (Ca2+) release channel required for skeletal muscle excitation–contraction (EC) coupling. RyR1 function modulated by proteins that bind to its large cytoplasmic scaffold domain, including FK506 binding protein (FKBP12) and PKA. PKA activated during sympathetic nervous system (SNS) stimulation. We show phosphorylation of at Ser2843 activates releasing FKBP12. When FKB12 bound RyR1, it inhibits stabilizing...
beta-Adrenergic receptor blockade is one of the most effective treatments for heart failure, a leading cause mortality worldwide. The use beta-adrenergic blockers in patients with failure counterintuitive, however, because they are known to decrease contractility normal hearts. ryanodine (RyR2) on cardiac sarcoplasmic reticulum key calcium release channel required excitation-contraction coupling. In failing hearts, stoichiometry and function RyR2 macromolecular complex altered. Decreased...
The ryanodine receptor (RyR1)/calcium release channel on the sarcoplasmic reticulum of skeletal muscle is comprised four 565,000-dalton RyR1s, each which binds one FK506 binding protein (FKBP12). RyR1 required for excitation-contraction coupling in muscle. FKBP12, a cis-trans peptidyl-prolyl isomerase, normal gating channel. In absence channels exhibit increased frequency, suggesting that FKBP12 "stabilizes" open and closed states. We now show substitution Gly, Glu, or Ile Val2461 prevents...
<title>Abstract</title> When accompanied by excessive exposure to the stressors, pregnancy may result in prenatal depression, that has turn negative influence on offspring’s brain. Mirtazapine, among other antidepressants, is commonly used treat depression. Even though mirtazapine generally considered safe for pregnant women, its effect offspring brain have not been sufficiently investigated. The present study aimed examine effects of chronic unpredictable stress (CUS) pregestational rats,...
The synergic effect of luminal Ca2+, cytosolic and adenosine triphosphate (ATP) on activation cardiac ryanodine receptor (RYR2) channels was examined in planar lipid bilayers. dose–response RYR2 gating activity to ATP characterized at a diastolic Ca2+ concentration 100 nM over range concentrations and, vice versa, 1 mM concentrations. Low level (1 mM) significantly increased the affinity channel for but without substantial channel. Higher levels (8–53 markedly amplified effects by...
Dantrolene is an intra-cellularly acting skeletal muscle relaxant used for the treatment of rare genetic disorder, malignant hyperthermia (MH). In most cases, MH susceptibility caused by dysfunction ryanodine receptor (RyR1) harboring one nearly 230 single-point mutations. The therapeutic effect dantrolene result a direct inhibitory action on RyR1 channel, thus suppressing aberrant Ca2+ release from sarcoplasmic reticulum. Despite almost identical dantrolene-binding sequence exits in all...
The sarcoplasmic reticulum (SR) in cardiac muscle is suggested to act as a dynamic storage for Zn2+ release and reuptake, albeit it primarily implicated the Ca2+ signaling required cycle. A large from SR mediated by ryanodine receptor (RYR2), while this has prominent conductance vivo, also conducts other divalent cations vitro. Since permeant Mg2+ have similar physical properties, we tested if RYR2 channel Zn2+. Using method of planar lipid membranes, evidenced that permeable with...
Abstract Aim: Two or more RYR2 channels reconstituted into a bilayer lipid membrane (BLM) can open and close either independently (single gating) simultaneously (coupled gating). The coupled gating phenomenon has been suggested as an attractive candidate for termination mechanism of Ca 2+ release from the sarcoplasmic reticulum, required periodic contraction relaxation cardiac muscle. Methods: Using method reconstitution channel BLM, we investigated potential effect luminal on stability...
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a highly arrhythmogenic syndrome triggered by stress, primarily linked to gain-of-function point mutations in the cardiac ryanodine receptor (RyR2). Flecainide, as an effective therapy for CPVT, known blocker of surface-membrane Na+ channel, also affecting intracellular RyR2 channel. The therapeutic relevance flecainide-RyR2 interaction remains controversial, flecainide blocks only current flowing opposite direction...