Russian Journal of Physiology

Специальный выпуск Российского физиологического журнала им. И.М. Сеченова посвящен рассмотрению вопросов механизмов регуляции функций висцеральных систем человека и животных в норме и патологии, что является одним из наиболее актуальных и динамично развивающихся направлений современной физиологии и медицины.

Neurons of sympathetic pre- and paravertebral ganglia differ in their electrophysiological properties, which contributes to their involvement of different functions. There are two main electrophysiological types of sympathetic ganglionic neurons in various mammals: phasic and tonic. The development of modern research methods, including patch clamp, made it possible to clarify previously obtained information on the main electrophysiological characteristics of neurons by puncturing the membrane using intracellular thin glass microelectrodes. Different features of sympathetic neuron firing are the result of differential expression of voltage-gated ion channels associated with different currents: incoming I_Na (tetrodotoxin-sensitive and -insensitive sodium), I_Ca (calcium), I_H (hyperpolarization-activated non-selective cation current), I_CaCl (calcium-dependent chloride current), as well as outgoing I_DR (delayed rectifier), I_AHP (after-hyperpolarization), I_A (fast outward potassium), I_M (slowly activating, non-inactivated outward current). This review describes the contribution of different channels to the excitability of sympathetic neurons, their changes in postnatal ontogenesis, as well as changes in the electrophysiological characteristics of ganglionic neurons in pathological processes.

Increased intestinal pain sensitivity (intestinal hyperalgesia) may be a consequence of intestinal inflammation or experienced stress. Both conditions are thought to be associated with a dysfunction of the basolateral amygdala (BLA), since they are accompanied by it’s neurochemical and molecular rearrangements. However, the accompanying changes in the neuronal mechanisms of BLA-executed control of visceral nociception and their possible specificity for post-inflammatory and stress-induced hyperalgesia remain unclear. The aim of the study was to compare the changes in the functional properties of visceral pain-responsive BLA neurons and their modulation by the infralimbic area of the medial prefrontal cortex (IL) that occur after intestinal inflammation or stress. The work was performed on male Wistar rats: 1) control, 2) subjected to experimental colitis and 3) subjected to prolonged emotional-painful stress. In animals from different groups, in awake state the intestinal hyperalgesia was assessed by recording the noxious colorectal distension (CRD)-induced visceromotor response, and under general anesthesia the microelectrode recording of the background impulse activity of BLA neurons and their responses to CRD before and after IL electrical stimulation was performed. It was found that rats from the postcolitis and stressed groups demonstrate intestinal hyperalgesia, which is more pronounced after stress. The postcolitis state is associated with a decrease, and the stressed state – with an increase in the background activity frequency of BLA neurons. It was shown for the first time that in both cases the BLA neurons that respond to CRD with excitation or inhibition increase their reactivity to the stimulating action of IL. The postcolitis period is characterized by an increase in the IL activating effect on the CRD-inhibited BLA neurons, whereas the poststress period is characterized by an increase in the IL-induced stimulation of excitated and inhibited nociceptive cells. The neuronal alterations revealed in the BLA may lead to the disturbances in the amygdala-executed control of the sensory and emotional components of visceral pain that are inherent to postinflammatory or stress-induced intestinal hyperalgesia, being thus a specific target for the treatment of such conditions in the clinic.

In different periods of postnatal development, the components of the autonomic nervous system, including specific receptors and neurotransmitters involved in controlling the functions of the cardiovascular system, are characterized by significant dynamics and variability. In humans and animals, α₂-adrenergic receptors (α₂-AR) and hyperpolarization-activated current (If) are widespread and participate in the regulation of many functions, but their modulating role at the stages of formation and development of adrenergic regulation of the developing heart has not been sufficiently studied. The study was conducted on isolated hearts of 1-, 3-week-old and adult sexually mature white rats. The heart rate and coronary flow (CF) of a Langendorff isolated rat heart were studied upon activation of α₂-AR clonidine hydrochloride (10^-6 M) against the background of If block ZD7288 (10^-9 M, 10^-5 M). In the group of newborn rat pups, α₂-AR activation causes a multidirectional change in CF, and against the background of If blockade (10^-9 M) causes a significant increase in CF, and against the background of If blockade (10^-5 M), a multidirectional change in CF is observed. In the group of 3-week-old rat pups, α₂-AR stimulation reduces CF, and against the background of preliminary If blockade, CF dynamics changes to positive. In adult rats, activation of α₂-AR against the background of If blockade causes a decrease in CF. The α₂-AR agonist causes a multidirectional change in heart rate in groups of newborn and adult rats, only in 3-week-old rats there is a decrease in heart rate. Stimulation of α₂-AR against the background of If blockade does not change the dynamics of heart rate in the group of 3-week-old rats, and cancels only multidirectional changes in adult and newborn rat's heart rate, causing a decrease in heart rate, and an increase in heart rate in newborn rats. The obtained results show that α₂-adrenergic regulation of the heart is modulated by If, the degree and direction of effects depends on the level of formation of sympathetic innervation of the heart.

Irritable bowel syndrome (IBS) is a functional, multifactorial gastrointestinal disorder that is characterized by impaired intestinal motility and visceral hypersensitivity. The aim of the study was to analyze the effect of H₂S and NO on spontaneous contractions of the jejunum in a rat model of IBS. The IBS was induced by neonatal maternal deprivation and verified by assessing visceral hypersensitivity. Spontaneous contractions of an isolated rat jejunum were recorded under isometric conditions. In a rat model of IBS, the amplitude of spontaneous contractions and the tonus were lower than in the control group, without changing the frequency of spontaneous contractions. The H₂S donor, sodium hydrosulfide (NaHS), had an inhibitory effect on jejunum contractions in the control, but this effects of NaHS were not manifested in the IBS group. The NO donor, sodium nitroprusside (SNP), caused inhibition of the amplitude in both groups, reduced the inhibitory effects of NaHS in the control group, while in the IBS group the effects of NaHS were not observed. The nitric oxide synthase (NOS) inhibitor, L-NAME, increased the amplitude of spontaneous contractions in both groups, with more pronounced effects in the IBS group. Under conditions of NOS inhibition, the inhibitory effect of NaHS on the amplitude of spontaneous contractions was restored in the IBS group. In the IBS group, the expression of cystathionine-β-synthase (CBS), the level of sulfides and the activity of H₂S-synthesizing enzymes in the rat jejunum tissues were lower, while the expression of nNOS and the concentration of NO metabolites were increased compared to the control. It has been suggested that in IBS, due to excessive NO synthesis, changes occur in the signaling pathways and/or targets through which H₂S acts, which leads to changes in jejunal motility in IBS and causes symptoms of increased peristalsis in IBS with diarrhea (IBS-D).

Arterial hypertension (AH) is the leading modifying risk factor for cardiovascular mortality. Systemic or pulmonary AH is also a significant factor stimulating the development of atrial fibrillation (AF). The pathophysiological mechanisms underlying the mutually reinforcing relationship between AH and AF are multifaceted and are due to structural, biochemical, and electrical remodeling of the atria. About 20% of AF cases are caused by the development of ectopic activity in the structures of the right atrium (RA), including the natural dominant pacemaker of the heart – the sinoatrial node (SAN), as well as the arrhythmogenic myocardium of the vena cava wall. The mechanisms stimulating the development of profibrillatory foci in the right atrium under mechanical action caused by AH remain poorly understood. The aim of this work was to study the mechanical effects on the electrophysiological properties of vulnerable zones of the RA myocardium and its susceptibility to proarrhythmic cholinergic effects. The experiments were performed using isolated tissue preparations of the right atrium of Wistar rats (400 ± 50 g, n = 16) and spontaneously hypertensive SHR rats (SBP: 180–220 mmHg, 300 ± 50 g, n = 10), including the sinoatrial node (SAN), the orifice and the distal part of the superior vena cava (SVC) and demonstrating automatic activity. Using the technique of multichannel microelectrode leads, simultaneous recording of the resting potential and spontaneous action potentials (AP) in the atrial and distal parts of the SVC was performed under control conditions, as well as under mechanical loading/stretching accompanied by the action of acetylcholine (ACH). The duration of AP in the SVC of hypertensive rats is significantly shorter than that of normotensive rats. The frequency of spontaneous AP in the SAN of SHR rats is lower than that of Wistar rats. The negative chronotropic effect caused by ACH in hypertensive rats is significantly greater than that of normotensive rats. Mechanical loading/stretching causes depolarization (up to –60 ± 5 mV), a decrease in AP amplitude, suppression of excitation conduction and excitation conduction blocks in the SVC. The above effects in the SVC of SHR rats develop with significantly less mechanical action than in Wistar rats. Mechanical loading/stretching increases the sinus rhythm in normotensive rat preparations (cycle length: –14 ± 3%, n = 16, p < 0.01), but causes its decrease in SHR rat preparations (+20 ± 9%, p < 0.01). Mechanical stimulation enhances the negative chronotropic effect of ACH. This enhancement is significantly more pronounced in SHR rats than in normotensive animals: under loading/stretching, ACH suppresses sinus rhythm in 100% of experiments in SHR and only in 50% in normotensive rats. Under control conditions, the RA myocardium of normotensive rats and SHRs demonstrates different bioelectrical properties and different sensitivity to ACH. The SAN and SVC in SHRs are more sensitive to mechanical effects. Mechanical stretching/loading increases the sensitivity of the SAN to choline stimulation. AH, due to increased sensitivity to ACH during myocardial stretching, promotes the formation of an arrhythmogenic substrate in the structures of the right atrium.

One of the most pressing issues in visceral physiology is the investigation of the molecular mechanisms behind pain signal interoception. Chronic abdominal pain is a type of pain sensitivity that arises during gastrointestinal disorders and frequently persists after they are healed. Abdominal pain syndrome is caused by molecular alterations in the intestinal wall, the specifics of which are still unknown. TRPV1 and TRPA1 are transient receptor potential (TRP) channels found in enteric nervous system nerve cells that contribute to the development of visceral pain and hypersensitivity perception. The rat colon's uneven distribution of channels along its proximal-distal axis suggests they may be involved in the initial stages of abdominal pain sensitivity. The goal of the present study was to evaluate segment-specific alterations in TRPV1 and TRPA1 channel levels after inflammation is initiated by a single lipopolysaccharide (LPS) dose. The study used the "cold and hot plate" pain sensitivity test, morphometric analysis methods, recording of electrophysiological parameters in the USsing chamber, and Western blotting to assess the TRPA1 and TRPV1 protein expression. The results of this research show that a unitary administration of LPS leads to diminished TRPA1 levels in both the ascending and descending colons. No variations in TRPV1 levels were found in the ascending colon, but a significant rise was recorded in the descending colon. There were no observed changes in nociception in "cold and hot plate" test. Thus, a segment-specific alteration in the levels of TRPA1 and TRPV1 channels was established in the direct model of LPS toxicity.