Presynaptic External Calcium Signaling Involves the Calcium-Sensing Receptor in Neocortical Nerve Terminals

Nerve terminal invasion by an axonal spike activates voltage-gated channels, triggering calcium entry, vesicle fusion, and release of neurotransmitter. Ion channels activated at the terminal shape the presynaptic spike and so regulate the magnitude and duration of calcium entry. Consequently characterization of the functional properties of ion channels at nerve terminals is crucial to understand the regulation of transmitter release. Direct recordings from small neocortical nerve terminals have revealed that external [Ca(2+)] ([Ca(2+)](o)) indirectly regulates a non-selective cation channel (NSCC) in neocortical nerve terminals via an unknown [Ca(2+)](o) sensor. Here, we identify the first component in a presynaptic calcium signaling pathway.By combining genetic and pharmacological approaches with direct patch-clamp recordings from small acutely isolated neocortical nerve terminals we identify the extracellular calcium sensor. Our results show that the calcium-sensing receptor (CaSR), a previously identified G-protein coupled receptor that is the mainstay in serum calcium homeostasis, is the extracellular calcium sensor in these acutely dissociated nerve terminals. The NSCC currents from reduced function mutant CaSR mice were less sensitive to changes in [Ca(2+)](o) than wild-type. Calindol, an allosteric CaSR agonist, reduced NSCC currents in direct terminal recordings in a dose-dependent and reversible manner. In contrast, glutamate and GABA did not affect the NSCC currents.Our experiments identify CaSR as the first component in the [Ca(2+)](o) sensor-NSCC signaling pathway in neocortical terminals. Decreases in [Ca(2+)](o) will depress synaptic transmission because of the exquisite sensitivity of transmitter release to [Ca(2+)](o) following its entry via voltage-activated Ca(2+) channels. CaSR may detects such falls in [Ca(2+)](o) and increase action potential duration by increasing NSCC activity, thereby attenuating the impact of decreases in [Ca(2+)](o) on release probability. CaSR is positioned to detect the dynamic changes of [Ca(2+)](o) and provide presynaptic feedback that will alter brain excitability

Can a Sports Team-based Lifestyle Program (Hockey Fans In Training) Improve Weight In Overweight Men?

The issue of gender is often neglected when planning and implementing chronic disease prevention and management strategies. Football Fans in Training (FFIT) — a gender-sensitized, weight loss and healthy living program for men delivered via professional football clubs — has been shown to be highly effective in helping overweight/obese men lose weight and improve their health risk. PURPOSE: To examine the potential for new male-friendly, physical activity and healthy living program — Hockey Fans in Training (Hockey FIT) — to help overweight/obese men decrease their weight, waist circumference (WC), and body mass index (BMI), after 12 weeks. METHODS: A pilot, pragmatic randomized controlled trial (RCT) whereby male fans (35-65 years; BMI ≥ 28 kg/m2) of 2 Junior A hockey clubs (Ontario, Canada) were randomized to either the intervention (Hockey FIT) or comparator (wait-list control). Hockey FIT involved 12 weekly, 90-minute group sessions delivered by trained coaches using club facilities. Each session combined classroom activities, including evidence- based behaviour change techniques (e.g., self-monitoring, goal setting) and healthy eating advice (e.g., reducing portions), with physical activity training. Lifestyle prescriptions, including incremental step count targets, were also prescribed each week. We examined between-group differences in mean weight loss, WC, and BMI using linear mixed effects regression models that accounted for club and age. RESULTS: Baseline characteristics were similar between groups [total N = 80, median (interquartile range) — i) age: 48.0 (17.0) years; ii) weight: 112.2 (23.2) kg; iii) WC: 119.3 (13.5) cm; iv) BMI: 35.1 (6.3) kg/m2]. Of the 40 men in the Hockey FIT group, 30 (75%) attended at least 6 sessions. At 12 weeks, the Hockey FIT group lost more weight than the control group [difference between groups in mean weight change (control is reference): -3.6 (95% confidence interval: -5.2 to -1.9) kg, p<0.001]. The Hockey FIT group also saw greater reductions in WC and BMI, when compared to the control group [difference between groups in mean i) WC: -2.8 (-5.0 to -0.6) cm, p=0.01; ii) BMI: -0.9 (-1.4 to -0.4) kg/m2, p<0.001]. CONCLUSION: Hockey FIT has the potential to help overweight/obese men lose weight and improve health risk. A definite RCT is warranted with long-term follow-up

Can a Sports Team-based Lifestyle Program (Hockey Fans In Training) Improve Weight In Overweight Men?

The issue of gender is often neglected when planning and implementing chronic disease prevention and management strategies. Football Fans in Training (FFIT) — a gender-sensitized, weight loss and healthy living program for men delivered via professional football clubs — has been shown to be highly effective in helping overweight/obese men lose weight and improve their health risk. PURPOSE: To examine the potential for new male-friendly, physical activity and healthy living program — Hockey Fans in Training (Hockey FIT) — to help overweight/obese men decrease their weight, waist circumference (WC), and body mass index (BMI), after 12 weeks. METHODS: A pilot, pragmatic randomized controlled trial (RCT) whereby male fans (35-65 years; BMI ≥ 28 kg/m2) of 2 Junior A hockey clubs (Ontario, Canada) were randomized to either the intervention (Hockey FIT) or comparator (wait-list control). Hockey FIT involved 12 weekly, 90-minute group sessions delivered by trained coaches using club facilities. Each session combined classroom activities, including evidence- based behaviour change techniques (e.g., self-monitoring, goal setting) and healthy eating advice (e.g., reducing portions), with physical activity training. Lifestyle prescriptions, including incremental step count targets, were also prescribed each week. We examined between-group differences in mean weight loss, WC, and BMI using linear mixed effects regression models that accounted for club and age. RESULTS: Baseline characteristics were similar between groups [total N = 80, median (interquartile range) — i) age: 48.0 (17.0) years; ii) weight: 112.2 (23.2) kg; iii) WC: 119.3 (13.5) cm; iv) BMI: 35.1 (6.3) kg/m2]. Of the 40 men in the Hockey FIT group, 30 (75%) attended at least 6 sessions. At 12 weeks, the Hockey FIT group lost more weight than the control group [difference between groups in mean weight change (control is reference): -3.6 (95% confidence interval: -5.2 to -1.9) kg, p<0.001]. The Hockey FIT group also saw greater reductions in WC and BMI, when compared to the control group [difference between groups in mean i) WC: -2.8 (-5.0 to -0.6) cm, p=0.01; ii) BMI: -0.9 (-1.4 to -0.4) kg/m2, p<0.001]. CONCLUSION: Hockey FIT has the potential to help overweight/obese men lose weight and improve health risk. A definite RCT is warranted with long-term follow-up