Exercise training is currently recommended in the management of mild hypertension, but the relationship between training and ventricular arrhythmias has never been investigated in hypertensive subjects. Forty hypertensive sportsmen were studied by means of 24-h ECG Holter monitoring and the results were compared with those obtained in 40 sedentary hypertensives, 40 normotensive sportsmen and 40 normotensive sedentary subjects. Among the hypertensive sportsmen 82.5% exhibited at least one ventricular extrasystole and 32.5% complex forms of ectopy, a prevalence higher than that observed in the sedentary hypertensives (50% and 17.5%; P = 0.002). In the normotensive sportsmen the prevalence of ventricular arrhythmias (62.5% and 22.5%) was lower than that in the hypertensive sportsmen, but the difference was not statistically significant. During a training session the prevalence of ventricular ectopy was similar in the two groups of trained individuals. Among the hypertensive sportsmen no correlation was found between the severity of ventricular arrhythmias and the degree of left ventricular hypertrophy and performance. The results of the present study suggest that exercise training may enhance left ventricular vulnerability in hypertensive subjects. Whether subjects who manifest complex ventricular arrhythmias should continue to train remains a matter for individual judgement.

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The NMDA receptor (NMDAR) is a ubiquitously expressed glutamate-gated ion channel that plays key roles in brain development and function. Not surprisingly, a variety of disease-associated variants have been identified in genes encoding NMDAR subunits. A critical first step to assess whether these variants contribute to their associated disorder is to characterize their effect on receptor function. However, the complexity of NMDAR function makes this challenging, with most variants typically altering multiple functional properties. At synapses, NMDARs encode presynaptic activity to carry a charge transfer that alters membrane excitability and a Ca2+ influx that has both short- and long-term signaling actions. Here, we characterized epilepsy-associated variants in GluN1 and GluN2A subunits with various phenotypic severity. To capture the dynamics of NMDAR encoding, we applied 10 glutamate pulses at 10 Hz to derive a charge integral. This encoding assay is advantageous since it incorporates multiple gating parameters, activation, deactivation, and desensitization, into a single value. We then integrated this encoding with Mg2+ block and Ca2+ influx using fractional Ca2+ currents to generate indices of charge transfer and Ca2+ transfer over wide voltage ranges. This approach yields consolidated parameters that can be used as a reference to normalize allosteric modulation and has the potential to speed up future bench to bedside methods of investigating variants to determine patient treatment.

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