Loss-of-activity-mutation in the cardiac chloride-bicarbonate exchanger AE3 causes short QT syndrome

Mutations in potassium and calcium channel genes have been associated with cardiac arrhythmias. Here, Jensen et al. show that an anion transporter chloride-bicarbonate exchanger AE3 is also responsible for the genetically-induced mechanism of cardiac arrhythmia, suggesting new therapeutic targets for this diseas

L-type Ca2+ channels in the heart: Structure and regulation

This review analyzes the structure and regulation mechanisms of voltagedependent L-type Ca2+ channel in the heart. L-type Ca2+ channels in the heart are composed of four different polypeptide subunits, and the pore-forming subunit a1 is the most important part of the channel. In cardiac myocytes, Ca2+ enter cell cytoplasm from extracellular space mainly through L-type Ca2+ channels; these channels are very important system in heart Ca2+ uptake regulation. L-type Ca2+ channels are responsible for the activation of sarcoplasmic reticulum Ca2+ channels (RyR2) and force of muscle contraction generation in heart; hence, activity of the heart depends on L-type Ca2+ channels. Phosphorylation of channel-forming subunits by different kinases is one of the most important ways to change the activity of L-type Ca2+ channel. Additionally, the activity of L-type Ca2+ channels depends on Ca2+ concentration in cytoplasm. Ca2+ current in cardiac cells can facilitate, and this process is regulated by phosphorylation of L-type Ca2+ channels and intracellular Ca2+ concentration. Disturbances in cellular Ca2+ transport and regulation of L-type Ca2+ channels are directly related to heart diseases, life quality, and life span

Kalcio jonų įtaka sensorinių neuronų vystymuisi ir jų atsakams į semaforinus

Biologijos katedraVytauto Didžiojo universiteta

L-type Ca2+ channels in the heart: structure and regulation

Šiame apžvalginiame straipsnyje analizuojama įtampos valdomų širdies L-tipo Ca2+ kanalų struktūra bei jų reguliacijos mechanizmai. Širdies L-tipo Ca2+ kanalai sudaryti iš keturių skirtingų baltyminių subvienetų, tarp kurių svarbiausias yra kanalo porą suformuojantis subvienetas a1. Širdies ląstelių L-tipo Ca2+ kanalai yra pagrindinis Ca2+ jonų patekimo kelias iš ląstelės išorės į citoplazmą ir yra labai svarbi širdies Ca2+ jonų apykaitą reguliuojanti sistema. Nuo šių kanalų aktyvumo priklauso sarkoplazminio tinklo RyR2 kanalų aktyvumas ir širdies raumens susitraukimo jėga, kartu ir širdies darbas. Vienas svarbiausių L-tipo Ca2+ kanalų aktyvumo reguliavimo būdų yra kanalą sudarančių baltymų fosforilinimas įvairiomis kinazėmis. L-tipo Ca2+ kanalų aktyvumas taip pat priklauso nuo Ca2+ jonų koncentracijos citoplazmoje. Širdies ląstelėms būdinga Ca2+ srovės fasilitacija ir šis procesas priklauso nuo L-tipo Ca2+ kanalų fosforilinimo bei Ca2+ jonų koncentracijos citoplazmoje. L-tipo Ca2+ kanalų reguliacijos sutrikimai ir ląstelinės Ca2+ jonų apykaitos pokyčiai yra tiesiogiai susiję su širdies ligomis, lemia gyvenimo kokybę bei trukmęThis review analyzes the structure and regulation mechanisms of voltage-dependent L-type Ca2+ channel in the heart. L-type Ca2+ channels in the heart are composed of four different polypeptide subunits, and the pore-forming subunit a1 is the most important part of the channel. In cardiac myocytes, Ca2+ enter cell cytoplasm from extracellular space mainly through L-type Ca2+ channels; these channels are very important system in heart Ca2+ uptake regulation. L-type Ca2+ channels are responsible for the activation of sarcoplasmic reticulum channels (RyR2) and force of muscle contraction generation in heart; hence, activity of the heart depends on L-type Ca2+ channels. Phosphorylation of channel-forming subunits by different kinases is one of the most important ways to change the activity of L-type Ca2+ channel. Additionally, the activity of L-type Ca2+ channels depends on Ca2+ concentration in cytoplasm. Ca2+ current in cardiac cells can facilitate, and this process is regulated by phosphorylation of L-type Ca2+ channels and intracellular Ca2+ concentration. Disturbances in cellular Ca2+ transport and regulation of L-type Ca2+ channels are directly related to heart diseases, life quality, and life spanKauno medicinos universiteto Kardiologijos instituta

Nerve growth factor and semaphorin 3A influence on sensory neuron axons growth

Introduction. It is known that nerve cells can regenerate their axons after damage to peripheral and in some cases central nerve system. However, axon growth over longer distances, especially in central nervous system is complicated. [...]Biologijos katedraKauno medicinos universitetas. Kardiologijos institutasVytauto Didžiojo universiteta

Dual-component voltage sensitivity of indocyanine green fluorescence in the heart

Background: Voltage-sensitive fluorescent dyes (VSDs) have been used in heart electrophysiological studies for over 30 years. Nevertheless, to date, VSDs have not yet been approved for clinical use. It was reported that the widely used fluorescent dye indocyanine green (ICG), which has FDA approval, exhibits voltage sensitivity in various tissues. Objective: The aim of this study was to explore the possibility of using ICG to monitor cardiac electrical activity. Methods: A standard glass microelectrode and optical mapping, using a near-infrared ICG fluorescent dye, were used to simultaneously record electrical action potential (AP) and optical signal (OS) in a Langendorff-perfused rabbit heart that was fully stopped. Results: We showed the first successful detection of voltage sensitivity of the ICG dye in a heart. The ICG OS is not caused by contraction or by Ca2+ transients, and reliably follows the AP changes induced by pharmacological compounds. The ICG OS has a dual-component (fast and slow) response to membrane potential changes that accurately tracks the time of electrical signal propagation but clearly differ in their kinetics and voltage-sensitive spectral properties. The voltage-sensitive fluorescence of ICG dye was not high relative to the fluorescence of standard VSDs. However, after averaging, the good signal-to-noise ratio (> 20 dB) of ICG rendered its signal suitable for observing cardiac electrical activity. Conclusions: Our research confirms that ICG is a voltage-sensitive dye with a dual-component (fast and slow) response to membrane potential changes. We suggest that it can be used as a tool for examining excitation wave propagation in the heart

Metabolic Inhibition Induces Transient Increase of L-type Ca²⁺ Current in Human and Rat Cardiac Myocytes

Metabolic inhibition is a common condition observed during ischemic heart disease and heart failure. It is usually accompanied by a reduction in L-type Ca2+ channel (LTCC) activity. In this study, however, we show that metabolic inhibition results in a biphasic effect on LTCC current (ICaL) in human and rat cardiac myocytes: an initial increase of ICaL is observed in the early phase of metabolic inhibition which is followed by the more classical and strong inhibition. We studied the mechanism of the initial increase of ICaL in cardiac myocytes during β-adrenergic stimulation by isoprenaline, a non-selective agonist of β-adrenergic receptors. The whole-cell patch–clamp technique was used to record the ICaL in single cardiac myocytes. The initial increase of ICaL was induced by a wide range of metabolic inhibitors (FCCP, 2,4-DNP, rotenone, antimycin A). In rat cardiomyocytes, the initial increase of ICaL was eliminated when the cells were pre-treated with thapsigargin leading to the depletion of Ca2+ from the sarcoplasmic reticulum (SR). Similar results were obtained when Ca2+ release from the SR was blocked with ryanodine. These data suggest that the increase of ICaL in the early phase of metabolic inhibition is due to a reduced calcium dependent inactivation (CDI) of LTCCs. This was further confirmed in human atrial myocytes where FCCP failed to induce the initial stimulation of ICaL when Ca2+ was replaced by Ba2+, eliminating CDI of LTCCs. We conclude that the initial increase in ICaL observed during the metabolic inhibition in human and rat cardiomyocytes is a consequence of an acute reduction of Ca2+ release from SR resulting in reduced CDI of LTCCs

Sema3A and NGF in regeneration of sensory axons

Regeneration of nervous system is complex and complicated process that involves neuron survival after injury as well as elongation of neurites and their guidance to final targets. Dorsal root ganglion (DRG) sensory neuron axon growth is highly impeded when they encounter neuronal growth cone-collapsing factor semaphorin3A (Sema3A) in both regeneration of adult nervous system and development of nervous system in embryonic stages. On the other hand, precise guidance of axon is mediated by many factors and increasing evidence shows that DRG axon development in both pathological and physiological conditions can be stimulated by nerve growth factor (NGF). The aim of this study was to evaluate the potential of increased NGF concentration to abolish Sema3A induced inhibitory responses in regenerating fifteen days old mouse embryo (e15) DRG axons in vitro. [...]Biologijos katedraLietuvos sveikatos mokslų universitetas. Kardiologijos institutasVytauto Didžiojo universiteta

Evaluation of the efficiency of DNA electrotransfer in vitro using high voltage and low voltage pulses

Introduction. The effectviveness of gene electrotransfer in vivo can be increased by using two types of electric pulses. First one is of short duration high voltage pulse (HV) that is mainly responsible for cell electroporation. The second one is of longer duration low voltage pulse (LV). It was shown in vivo that LV pulse governs DNA electrotransfer efficiency, presumbly by exerting electrophoretic forces that can interact with DNA and facilitate its translocation across the membrane into porated cells. [...]Biologijos katedraVytauto Didžiojo universiteta