Daily Resting Heart Rate Variability in Adolescent Swimmers during 11 Weeks of Training.

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.

Differences in the control of basal L-type Ca(2+) current by the cyclic AMP signaling cascade in frog, rat, and human cardiac myocytes.

ß-adrenergic receptors (ß-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 ß-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.

Src family protein tyrosine kinases modulate L-type calcium current in human atrial myocytes.

In the heart, L-type voltage dependent calcium channels (L-VDCC) provide Ca(2+) for the activation of contractile apparatus. The best described pathway for L-type Ca(2+) current (I(Ca,L)) modulation is the phosphorylation of calcium channels by cAMP-dependent protein kinase A (PKA), the activity of which is predominantly regulated in opposite manner by ß-adrenergic (ß-ARs) and muscarinic receptors. The role of other kinases is controversial and often depends on tissues and species used in the studies. In different studies the inhibitors of tyrosine kinases have been shown either to stimulate or inhibit, or even have a biphasic effect on I(Ca,L). Moreover, there is no clear picture about the route of activation and the site of action of cardiac Src family nonreceptor tyrosine kinases (Src-nPTKs). In the present study we used PP1, a selective inhibitor of Src-nPTKs, alone and together with different activators of I(Ca,L), and demonstrated that in human atrial myocytes (HAMs): (i) Src-nPTKs are activated concomitantly with activation of cAMP-signaling cascade; (ii) Src-nPTKs attenuate PKA-dependent stimulation of I(Ca,L) by inhibiting PKA activity; (iii) Gα(s) are not involved in the direct activation of Src-nPTKs. In this way, Src-nPTKs may provide a protecting mechanism against myocardial overload under conditions of increased sympathetic activity.

beta3-adrenergic receptor activation increases human atrial tissue contractility and stimulates the L-type Ca2+ current.

beta3-adrenergic receptor (beta3-AR) activation produces a negative inotropic effect in human ventricles. Here we explored the role of beta3-AR in the human atrium. Unexpectedly, beta3-AR activation increased human atrial tissue contractility and stimulated the L-type Ca2+ 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 beta3-AR agonists, SR58611 and BRL37344, and a beta3-AR partial agonist, CGP12177, stimulated I(Ca,L) in HAMs with nanomolar potency and a 60%-90% efficacy compared with isoprenaline. The beta3-AR agonists also increased contractility but with a much lower efficacy (approximately 10%) than isoprenaline. The beta3-AR antagonist L-748,337, beta1-/beta2-AR antagonist nadolol, and beta1-/beta2-/beta3-AR antagonist bupranolol were used to confirm the involvement of beta3-ARs (and not beta1-/beta2-ARs) in these effects. The beta3-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, beta3-ARs are positively coupled to L-type Ca2+ channels and contractility in human atrial tissues through a cAMP-dependent pathway.