scholarly journals Neuronal glucose metabolism sets cholinergic tone and controls thermo-regulated signaling at the neuromuscular junction

2021 ◽  
Author(s):  
Yan Tang ◽  
Haihong Zong ◽  
Hyokjoon Kwon ◽  
Yunping Qiu ◽  
Jacob B. Pessin ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Regulatory Networks ◽  
Cholinergic Neurons ◽  
Metabolic Energy ◽  
Cholinergic Signaling ◽  
Increase Energy Expenditure ◽  
Stress Responsiveness ◽  
Cholinergic Tone ◽  
Specific Deletion

Cholinergic and sympathetic counter-regulatory networks control numerous physiologic functions including learning/memory/cognition, stress responsiveness, blood pressure, heart rate and energy balance. As neurons primarily utilize glucose as their primary metabolic energy source, we generated mice with increased glycolysis in cholinergic neurons by specific deletion of the fructose-2,6-phosphatase protein TIGAR. Steady-state and stable isotope flux analyses demonstrated increased rates of glycolysis, acetyl-CoA production, acetylcholine levels and density of neuromuscular synaptic junction clusters with enhanced acetylcholine release. The increase in cholinergic signaling reduced blood pressure and heart rate with a remarkable resistance to cold-induced hypothermia. These data directly demonstrate that increased cholinergic signaling through the modulation of glycolysis has several metabolic benefits particularly to increase energy expenditure and heat production upon cold exposure.

scholarly journals STIM1–Ca2+ signaling modulates automaticity of the mouse sinoatrial node

2015 ◽  
Vol 112 (41) ◽  
pp. E5618-E5627 ◽  
Author(s):  
Hengtao Zhang ◽  
Albert Y. Sun ◽  
Jong J. Kim ◽  
Victoria Graham ◽  
Elizabeth A. Finch ◽  
...  
Keyword(s):  
Heart Rate ◽  
Sinoatrial Node ◽  
Membrane Surface ◽  
Surface Membrane ◽  
Autonomic Response ◽  
Sinus Arrest ◽  
Cholinergic Signaling ◽  
Ionic Fluxes ◽  
Cardiac Pacemaking ◽  
Specific Deletion

Cardiac pacemaking is governed by specialized cardiomyocytes located in the sinoatrial node (SAN). SAN cells (SANCs) integrate voltage-gated currents from channels on the membrane surface (membrane clock) with rhythmic Ca2+ release from internal Ca2+ stores (Ca2+ clock) to adjust heart rate to meet hemodynamic demand. Here, we report that stromal interaction molecule 1 (STIM1) and Orai1 channels, key components of store-operated Ca2+ entry, are selectively expressed in SANCs. Cardiac-specific deletion of STIM1 in mice resulted in depletion of sarcoplasmic reticulum (SR) Ca2+ stores of SANCs and led to SAN dysfunction, as was evident by a reduction in heart rate, sinus arrest, and an exaggerated autonomic response to cholinergic signaling. Moreover, STIM1 influenced SAN function by regulating ionic fluxes in SANCs, including activation of a store-operated Ca2+ current, a reduction in L-type Ca2+ current, and enhancing the activities of Na+/Ca2+ exchanger. In conclusion, these studies reveal that STIM1 is a multifunctional regulator of Ca2+ dynamics in SANCs that links SR Ca2+ store content with electrical events occurring in the plasma membrane, thereby contributing to automaticity of the SAN.

scholarly journals Maintained barostatic regulation of heart rate in digesting snakes (Boa constrictor)

2021 ◽  
Author(s):  
Tobias Wang ◽  
Augusto S. Abe ◽  
Ariavaldo P. Cruz-Neto ◽  
Denis Andrade ◽  
E.W. Taylor (Ted)
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Sodium Nitroprusside ◽  
Pressure Regulation ◽  
Chronotropic Response ◽  
Pharmacological Manipulation ◽  
Boa Constrictor ◽  
Cholinergic Tone ◽  
Autonomic Blockade ◽  
Chronotropic Effects

When snakes digest large meals, heart rate is accelerated by withdrawal of vagal tone and an increased non-adrenergic-non-cholinergic tone that seems to stem from circulating blood-borne factors exerting positive chronotropic effects. To investigate whether this tonic elevation of heart rate impairs the ability for autonomic regulation of heart during digestion, we characterised heart rate responses to pharmacological manipulation of blood pressure in the snake Boa constrictor through serial injections of sodium nitroprusside and phenylephrine. Both fasting and digesting snakes responded with a robust tachycardia to hypotension induced by sodium nitroprusside, with digesting snakes attaining higher maximal heart rates than fasting snakes. Both fasting and digesting snakes exhibited small reductions of the cardiac chronotropic response to hypertension, induced by injection of phenylephrine. All heart rate changes were abolished by autonomic blockade with the combination of atropine and propranolol. The digesting snakes retained the capacity for compensatory heart rate responses to hypotension, despite their higher resting values, and the upward shift of the barostatic response curve enable snakes to maintain the cardiac limb for blood pressure regulation.

scholarly journals Enhanced analgesic cholinergic tone after neuropathy

2020 ◽  
Author(s):  
Dhanasak Dhanasobhon ◽  
Maria-Carmen Medrano ◽  
Yunuen Moreno-Lopez ◽  
Sehrazat Kavraal ◽  
Charlotte Bichara ◽  
...  
Keyword(s):  
Sensory Processing ◽  
Mechanical Allodynia ◽  
Nicotinic Receptors ◽  
Pain Treatment ◽  
Cholinergic Neurons ◽  
Low Doses ◽  
Ache Inhibitors ◽  
Cholinergic Signaling ◽  
Cholinergic Tone ◽  
Spinal Cord Level

AbstractAt the spinal cord level, a tone of endogenous acetylcholine (ACh) modulates nociceptive sensory processing. Increasing the level of spinal ACh induces analgesia in naïve animals or in situation of acute pain in the clinics, but whether this is still the case in situations or models of chronic pain is controversial. Here, we demonstrate the persistence, and even increased impact of the analgesic cholinergic tone acting through nicotinic receptors in neuropathic mice. The neuropathy does not affect the number and properties of dorsal horn cholinergic neurons, proposed to be the source of spinal ACh. Subthreshold doses of acetylcholinesterase (AChE) inhibitors in sham animals become anti-allodynic in cuff mice suggesting that the alterations occur in the cholino-receptive neurons. Thus endogenous cholinergic signaling can be manipulated with low doses of drugs to relieve mechanical allodynia in animal neuropathy models. This opens new avenues with potentially fewer side effects for neuropathic pain treatment.

Caffeine and Placebo Expectation

2007 ◽  
Vol 21 (2) ◽  
pp. 91-99 ◽  
Author(s):  
Yunfeng Sun ◽  
Yinling Zhang ◽  
Ning He ◽  
Xufeng Liu ◽  
Danmin Miao
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Sleep Deprivation ◽  
Cognitive Performance ◽  
Cognitive Functions ◽  
Cardiovascular Regulation ◽  
Double Blind ◽  
Positive Effects ◽  
Pressure Tests ◽  
Healthy Males

Abstract. Caffeine placebo expectation seems to improve vigilance and cognitive performance. This study investigated the effect of caffeine and placebo expectation on vigilance and cognitive performance during 28 h sleep deprivation. Ten healthy males volunteered to take part in the double-blind, cross-over study, which required participants to complete five treatment periods of 28 h separated by 1-week wash-out intervals. The treatments were no substance (Control); caffeine 200 mg at 00:00 (C200); placebo 200 mg at 00:00 (P200); twice caffeine 200 mg at 00:00 and 04:00 (C200-C200); caffeine 200 mg at 00:00 and placebo 200 mg at 04:00 (C200-P200). Participants were told that all capsules were caffeine and given information about the effects of caffeine to increase expectation. Vigilance was assessed by a three-letter cancellation test, cognitive functions by the continuous addition test and Stroop test, and cardiovascular regulation by heart rate and blood pressure. Tests were performed bihourly from 00:00 to 10:00 of the second day. Results indicated that C200-P200 and C200-C200 were more alert (p < .05) than Control and P200. Their cognitive functions were higher (p < .05) than Control and P200. Also, C200-P200 scored higher than C200 in the letter cancellation task (p < .05). No test showed any significant differences between C200-P200 and C200-C200. The results demonstrated that the combination of caffeine 200 mg and placebo 200 mg expectation exerted prolonged positive effects on vigilance and cognitive performance.

Reduction in Pain Sensitivity from Pharmacological Elevation of Blood Pressure in Persons with Chronically Low Blood Pressure

2009 ◽  
Vol 23 (3) ◽  
pp. 104-112 ◽  
Author(s):  
Stefan Duschek ◽  
Heike Heiss ◽  
Boriana Buechner ◽  
Rainer Schandry
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Pain Sensitivity ◽  
Pain Threshold ◽  
Pain Perception ◽  
Drug Effects ◽  
Pressure Effects ◽  
Double Blind ◽  
Low Blood Pressure ◽  
Present Trial

Recent studies have revealed evidence for increased pain sensitivity in individuals with chronically low blood pressure. The present trial explored whether pain sensitivity can be reduced by pharmacological elevation of blood pressure. Effects of the sympathomimetic midodrine on threshold and tolerance to heat pain were examined in 52 hypotensive persons (mean blood pressure 96/61 mmHg) based on a randomized, placebo-controlled, double-blind design. Heat stimuli were applied to the forearm via a contact thermode. Confounding of drug effects on pain perception with changes in skin temperature, temperature sensitivity, and mood were statistically controlled for. Compared to placebo, higher pain threshold and tolerance, increased blood pressure, as well as reduced heart rate were observed under the sympathomimetic condition. Increases in systolic blood pressure between points of measurement correlated positively with increases in pain threshold and tolerance, and decreases in heart rate were associated with increases in pain threshold. The findings underline the causal role of hypotension in the augmented pain sensitivity related to this condition. Pain reduction as a function of heart rate decrease suggests involvement of a baroreceptor-related mechanism in the pain attrition. The increased proneness of persons with chronic hypotension toward clinical pain is discussed.

Sex Differences in Cardiovascular Reactivity

2009 ◽  
Vol 23 (2) ◽  
pp. 77-84 ◽  
Author(s):  
Matthew C. Whited ◽  
Kevin T. Larkin
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Sex Differences ◽  
Gender Roles ◽  
Cardiovascular Reactivity ◽  
Task Type ◽  
Conflict Task ◽  
Men And Women ◽  
Conflicting Evidence ◽  
Blood Pressure Responses

Sex differences in cardiovascular reactivity to stress are well documented, with some studies showing women having greater heart rate responses than men, and men having greater blood pressure responses than women, while other studies show conflicting evidence. Few studies have attended to the gender relevance of tasks employed in these studies. This study investigated cardiovascular reactivity to two interpersonal stressors consistent with different gender roles to determine whether response differences exist between men and women. A total of 26 men and 31 women were assigned to either a traditional male-oriented task that involved interpersonal conflict (Conflict Task) or a traditional female-oriented task that involved comforting another person (Comfort Task). Results demonstrated that women exhibited greater heart rate reactions than men independent of the task type, and that men did not display a higher reactivity than women on any measure. These findings indicate that sex of participant was more important than gender relevance of the task in eliciting sex differences in cardiovascular responding.

The Effects of a Caffeine Placebo and Experimenter Expectation on Blood Pressure, Heart Rate, Well-Being, and Cognitive Performance

2001 ◽  
Vol 6 (1) ◽  
pp. 15-25 ◽  
Author(s):  
Harald Walach ◽  
Stefan Schmidt ◽  
Yvonne-Michelle Bihr ◽  
Susanne Wiesch
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Cognitive Task ◽  
Well Being ◽  
Control Group ◽  
Double Blind ◽  
Main Effect ◽  
The Difference ◽  
Being There ◽  
To Receive

We studied the effect of experimenter expectations and different instructions in a balanced placebo design. 157 subjects were randomized into a 2 × 4 factorial design. Two experimenters were led to expect placebos either to produce physiological effects or not (pro- vs. antiplacebo). All subjects except a control group received a caffeine placebo. They were either made to expect coffee, no coffee, or were in a double-blind condition. Dependent measures were blood pressure, heart rate, well-being, and a cognitive task. There was one main effect on the instruction factor (p = 0.03) with the group “told no caffeine” reporting significantly better well-being. There was one main effect on the experimenter factor with subjects instructed by experimenter “proplacebo” having higher systolic blood pressure (p = 0.008). There was one interaction with subjects instructed by experimenter “proplacebo” to receive coffee doing worse in the cognitive task than the rest. Subjects instructed by experimenter “antiplacebo” were significantly less likely to believe the experimental instruction, and that mostly if they had been instructed to receive coffee. Contrary to the literature we could not show an effect of instruction, but there was an effect of experimenters. It is likely, however, that these experimenter effects were not due to experimental manipulations, but to the difference in personalities.

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