Aging is associated with mitochondrial dysfunction and alterations in heart function. A hallmark of mitochondrial dysfunction is the formation of highly conductive megachannels – mitochondrial permeability transition pores (mPTPs), the prevention of which may be an effective method of cardioprotection. Moderate exercise training reduces risk factors and protects the heart from ischemic damage. However, the effects of exercise training on cardiovascular function during aging still need to be studied. This study aimed to investigate the expression of genes encoding potential mPTP components and ATP-sensitive potassium (KATP) channel subunits in the heart during ageing and under conditions of moderate exercise training. mRNA expression levels were determined by reverse transcription and RT-PCR analysis. An increase in the expression of two mPTP components in the heart of old rats was shown, namely: mRNA of the Vdac1 gene, which encodes a voltage-dependent anion channel 1 (VDAC1), by 2.7 times, and mRNA of the Ppif gene, which encodes cyclophilin D, by 2.7 times compared to adult animals, as well as a significant decrease in their expression during moderate exercise training, which is considered a mitoprotective effect. With aging, mRNA expression of structural subunits of mitochondrial (SUR1) and sarcolemmal (SUR2 and Kir6.2) KATP channels is reduced in heart tissues, indicating a weakening of cardioprotective potential. An increase in the expression of cardiac Kir6.2 and vascular Kir6.1 subunits, which form the channel's conduction pore, and the regulatory component SUR2, under training conditions, may contribute to an increase in the heart's resistance to ischemic effects and endurance to exercise training. At the same time, increased expression of the mitochondrial KATP channel subunit SUR1 may contribute to mitochondrial resistance to adverse factors. Thus, exercise training during aging promotes cardioprotection through modulation of KATP channels and restoration of mitochondrial function.
Genetic and paratypic factors largely determine the functional state of piglets. Among these factors, stress induced by weaning from the sow plays a dominant role. Despite previous research, the physiological response to this stress remains poorly understood. Our study aimed to determine the characteristics of piglets' physiological responses to the stress caused by weaning. Three groups of animals were formed based on the severity of their stress response: Group I was stress-resistant, Group II was weakly responsive, and Group III was strongly responsive. Piglets in all groups exhibited a stress response, as indicated by changes in hematological and physiological parameters. These changes generally occurred within the limits of moderate stress on the body's functional reserves and remained close to the physiological norm. Compared to animals in group III, piglets in groups I and II showed better immune response parameters against the background of stress. The biochemical parameters of the blood serum did not differ significantly at the time of weaning. Still, four days after the stress, the differences between the groups became more noticeable, indicating a response to the “weaning crisis.” By the ninth day, a tendency toward stabilization was observed. Stress caused by weaning piglets from sows was accompanied by changes in immune activity indicators and deviations in physiological parameters, particularly body temperature, respiratory rate, and pulse. Intergroup differences were mainly recorded on the fourth day after weaning. Thus, these results can justify practical approaches to minimizing the negative effects of stress during weaning, maintaining physiological stability, and improving piglets' overall health.
Combat traumatic brain injury (cTBI) is characterized by the complexity of pathogenetic mechanisms, caused by the combination of the action of factors of mine-blast damage with the psycho-emotional reaction of the body to stress. The consequences of cTBI are manifested in changes in electrogenesis and neurochemical parameters of functional and metabolic activity of the brain, one of the important factors of which is cerebral cortisol levels. Identifying the nature of these changes is necessary to improve the effectiveness of therapy and rehabilitation of combatants. The study aimed to identify the features of brain electrogenesis and its relationship with the temporal dynamics of cortisol levels in the blood serum and cerebrospinal fluid (CSF) of combatants with brain contusion after cTBI 23 patients with TBI were examined (10 in the acute and 13 in the intermediate periods after the injury), whose electroencephalograms (EEG) were recorded, and their visual, spectral, and coherent analyses were also performed. The cortisol levels were determined in CSF and serum by enzyme-linked immunosorbent assay. The EEG spectrograms revealed an increase in the spectral power of Δ-range oscillations in the frontotemporal and central brain regions with the development of the consequences of сTBI over time. The spectral power of β-range oscillations in the intermediate period after the injury decreased compared to the acute period. Cortisol levels in CSF and serum increased over time after cTBI. The level of the hormone in CSF in the acute period after trauma was positively correlated with the spectral power of the biopotentials of the Δ-, θ-, and β-ranges. In the intermediate period, the degree of correlation of cortisol concentration with the spectral power of the biopotentials of the θ- and Δ-ranges decreased, but increased in the β-range. Thus, the EEG of combatants revealed an increase in the spectral power of slow rhythms with impaired intra- and interhemispheric neural communication, an increase in cortisol levels in CSF and serum over time, and its positive correlations with the biopotentials of the β-ranges against the background of a weakening, with the biopotentials of slow rhythms.
Potassium channels represent one of the most functionally diverse families of neuronal ion channels, critically shaping membrane excitability, action potential kinetics, neurotransmitter release, and the restoration of resting membrane potential. This review summarizes current knowledge on the molecular architecture and functional specialization of major K+ channel classes in the nervous system, including voltage-gated (Kv), tandem-pore (K2P), inwardly rectifying (Kir), and calcium-activated (KCa) channels. Particular emphasis is placed on the structural and functional properties of Kv1 family subunits, especially Kv1.2, their precise subcellular distribution (soma, dendrites, axon initial segment, presynaptic terminals), and their role in regulating action potential threshold, presynaptic Ca2+ entry, and neurotransmitter release. We discuss the mechanisms of hypoxic sensitivity of K+ channels and the consequences of oxygen deficiency for neuronal function. Hypoxia modulates the activity of multiple K+ channel types, leading either to hyperpolarization via KATP channel opening or to depolarization due to inhibition of Kv channels and subsequent Na+ accumulation. Dysregulation of Kv1.2 and related subunits during hypoxia and ischemia contributes to impaired Ca2+ homeostasis, enhanced neuronal excitability, glutamate-dependent excitotoxicity, and structural damage. The involvement of Kv channels in hypoxic pulmonary vasoconstriction and the downregulation of Kv1.2/Kv1.5 expression under chronic hypoxia in pulmonary artery smooth muscle cells are also highlighted. Finally, we describe the pathophysiological relevance of K+ channels in neurological disorders, including epilepsy, ischemic stroke, spinal cord injury, demyelinating diseases, and neurodegeneration, and outline therapeutic perspectives of pharmacological modulation of Kv, Kir, KCa, and K2P channels in brain hypoxia and hypoxic-ischemic injury.
On September 22, the Honored Worker of Science and Technology of Ukraine, Doctor of Medical Sciences, Professor, Oleksiy Antonovich Shandra, would have turned 75. However, we do not congratulate him, but only remember him. And there is someone to remember, because he devoted his entire life to medicine, medical science, raised more than one generation of students who continue the work of the Teacher. About Professor O.A. Shandra, despite his absence from us, it is impossible to speak in the past tense. Because the Teacher, who gave many of us, now alive and actively working, a ticket to life, is forever in the heart of each of us! He raised a wonderful galaxy of doctors and scientists and put his great soul into each of us.
