β 3 -adrenergic receptor (β 3 -AR) activation produces a negative inotropic effect in human ventricles. Here we explored the role of β 3 -AR in the human atrium. Unexpectedly, β 3 -AR activation increased human atrial tissue contractility and stimulated the L-type Ca 2+ channel current (I Ca,L ) in isolated human atrial myocytes (HAMs). Right atrial tissue specimens were obtained from 57 patients undergoing heart surgery for congenital defects, coronary artery diseases, valve replacement, or heart transplantation. The I Ca,L and isometric contraction were recorded using a whole-cell patch-clamp technique and a mechanoelectrical force transducer. Two selective β 3 -AR agonists, SR58611 and BRL37344, and a β 3 -AR partial agonist, CGP12177, stimulated I Ca,L in HAMs with nanomolar potency and a 60%-90% efficacy compared with isoprenaline. The β 3 -AR agonists also increased contractility but with a much lower efficacy (~10%) than isoprenaline. The β 3 -AR antagonist L-748,337, β 1 -/β 2 -AR antagonist nadolol, and β 1 -/β 2 -/β 3 -AR antagonist bupranolol were used to confirm the involvement of β 3 -ARs (and not β 1 -/β 2 -ARs) in these effects. The β 3 -AR effects involved the cAMP/PKA pathway, since the PKA inhibitor H89 blocked I Ca,L stimulation and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) strongly increased the positive inotropic effect. Therefore, unlike in ventricular tissue, β 3 -ARs are positively coupled to L-type Ca 2+ channels and contractility in human atrial tissues through a cAMP-dependent pathway.
β-adrenergic receptors (β-ARs) mediate the positive inotropic effects of catecholamines by cAMP-dependent phosphorylation of the L-type Ca(2+) channels (LTCCs), which provide Ca(2+) for the initiation and regulation of cell contraction. The overall effect of cAMP-modulating agents on cardiac calcium current (I Ca,L) and contraction depends on the basal activity of LTCCs which, in turn, depends on the basal activities of key enzymes involved in the cAMP signaling cascade. Our current work is a comparative study demonstrating the differences in the basal activities of β-ARs, adenylyl cyclase, phosphodiesterases, phosphatases, and LTCCs in the frog and rat ventricular and human atrial myocytes. The main conclusion is that the basal I Ca,L, and consequently the contractile function of the heart, is secured from unnecessary elevation of its activity and energy consumption at the several "checking-points" of cAMP-dependent signaling cascade and the loading of these "checking-points" may vary in different species and tissues.
Adolescent athletes are particularly vulnerable to stress. The current study aimed to monitor one of the most popular and accessible stress markers, heart rate variability (HRV), and its associations with training load and sleep duration in young swimmers during an 11-week training period to evaluate its relevance as a tool for monitoring overtraining. National-level swimmers (n = 22, age 14.3 ± 1.0 years) of sprint and middle distance events followed individually structured training programs prescribed by their swimming coach with the main intention of preparing for the national championships. HRV after awakening, during sleep and training were recorded daily. There was a consistent ~4.5% reduction in HRV after 3–5 consecutive days of high (>6 km/day) swimming volume, and an inverse relationship of HRV with large (>7.0 km/day) shifts in total training load (r = −0.35, p < 0.05). Day-to-day HRV did not significantly correlate with training volume or sleep duration. Taken together, these findings suggest that the value of HRV fluctuations in estimating the balance between the magnitude of a young athlete’s physical load and their tolerance is limited on a day-to-day basis, while under sharply increased or extended training load the lower HRV becomes an important indicator of potential overtraining.
Santykiškai didesnis raumenų susitraukimo jėgos sumažėjimas stimuliuojant raumenį mažais nei dideliais dažniais vadinamas mažų dažnių nuovargiu (MDN). Galimos šios MDN priežastys: raumeninės skaidulos sarkomerų ir elas-tinių komponentų irimas bei sumažėjęs iš sarkoplazminio tinklo išmetamų Ca 2+ kiekis. Nėra vienodos nuomonės dėl įvairių metabolitų poveikio raumenų susitraukimo funkcijai.Tyrimo tikslas — nustatyti adenozintrifosfato (ATP), fosfokreatino (PCr) ir neorganinio fosfato (P i ) poveikį priekinio blauzdos raumens mažų dažnių nuovargiui išemijos sąlygomis.Eksperimento metu buvo tiriami sveiki nesportuojantys 24—32 metų amžiaus vyrai (n = 10). Tiriamųjų raumuo iš-eminėmis sąlygomis vieną minutę buvo stimuliuojamas elektra (ES) tokiu dažniu, kuris sukelia 50% maksimaliosios raumens susitraukimo jėgos dydį. Registruoti rodikliai: priekinio blauzdos raumens susitraukimo jėga, sukelta 1, 15, 50 ir 100 Hz dažnio elektros stimuliavimu, bei ATP, PCr, P i koncentracija, nustatyta naudojant spektrometrą (Vi-vospec, Otsuka Elektronics, Fort Collins, Co) ir superlaidų horizontalų branduolių magnetinio rezonanso magnetą. Magneto galingumas — 2,9 T, cilindro skersmuo — 31 cm. Iš P i ir PCr koncentracijos pokyčių skirtumo nustatytas raumenų pH. Pagal 15 / 50 Hz stimuliavimo raumens susitraukimo jėgos santykio pokytį buvo vertinamas mažų dažnių nuovargis. Tyrimo rezultatai parodė, kad metabolinio nuovargio metu mažėjo visais (1—100 Hz) stimuliavimo dažniais sukelta priekinio blauzdos raumens susitraukimo jėga (p < 0,05). MDN tuoj po ES buvo mažas, tačiau reikšmingai padi-dėjo praėjus 24 valandoms po stimuliavimo (p < 0,05), kai tuo tarpu metaboliniai pokyčiai išnyko per 30 minučių po stimuliavimo. ATP koncentracija eksperimento metu nepakito. Išvada: po 1 minutės priekinio blauzdos raumens stimuliavimo išeminėmis sąlygomis PCr ir P i koncentracijos pokyčiai tiesioginio poveikio mažų dažnių nuovargiui neturėjo.
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