scholarly journals Time-of-day dependent changes in guinea pig bladder afferent mechano-sensitivity

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Stewart Christie ◽  
Vladimir Zagorodnyuk
Keyword(s):  
Circadian Rhythm ◽  
Guinea Pigs ◽  
Ex Vivo ◽  
Time Of Day ◽  
High Threshold ◽  
Afferent Activity ◽  
Night Time ◽  
Bladder Afferents ◽  
Low Threshold ◽  
Spinal Afferents

AbstractThe voiding of urine has a clear circadian rhythm with increased voiding during active phases and decreased voiding during inactive phases. Bladder spinal afferents play a key role in the regulation of bladder storage and voiding, but it is unknown whether they exhibit themselves a potential circadian rhythm. Therefore, this study aimed to determine the mechano- and chemo- sensitivity of three major bladder afferent classes at two opposite day-night time points. Adult female guinea pigs underwent conscious voiding monitoring and bladder ex vivo single unit extracellular afferent recordings at 0300 h and 1500 h to determine day-night modulation of bladder afferent activity. All guinea pigs voided a higher amount of urine at 1500 h compared to 0300 h. This was due to an increased number of voids at 1500 h. The mechano-sensitivity of low- and high-threshold stretch-sensitive muscular-mucosal bladder afferents to mucosal stroking and stretch was significantly higher at 1500 h compared to 0300 h. Low-threshold stretch-insensitive mucosal afferent sensitivity to stroking was significantly higher at 1500 h compared to 0300 h. Further, the chemosensitivity of mucosal afferents to N-Oleoyl Dopamine (endogenous TRPV1 agonist) was also significantly increased at 1500 h compared to 0300 h. This data indicates that bladder afferents exhibit a significant time-of-day dependent variation in mechano-sensitivity which may influence urine voiding patterns. Further studies across a 24 h period are warranted to reveal potential circadian rhythm modulation of bladder afferent activity.

scholarly journals Functional changes in low- and high-threshold afferents in obstruction-induced bladder overactivity

2019 ◽  
Vol 316 (6) ◽  
pp. F1103-F1113
Author(s):  
Vladimir P. Zagorodnyuk ◽  
Lauren J. Keightley ◽  
Simon J. H. Brookes ◽  
Nick J. Spencer ◽  
Marcello Costa ◽  
...  
Keyword(s):  
Guinea Pigs ◽  
Bladder Outlet Obstruction ◽  
Outlet Obstruction ◽  
High Threshold ◽  
Spontaneous Firing ◽  
Urinary Tract Symptoms ◽  
Different Types ◽  
Bladder Afferents ◽  
Low Threshold ◽  
Lower Urinary

Neural mechanisms of lower urinary tract symptoms in obstruction-induced bladder overactivity remain unclear. We made the first single unit recordings from different types of spinal afferents to determine the effects of bladder outlet obstruction in guinea pigs. A model of gradual bladder outlet obstruction in male guinea pigs was used to produce overactive bladder. Conscious voiding was assessed in metabolic cages, and micturition was recorded in anesthetized guinea pigs in vivo. Single unit extracellular recordings were made ex vivo from spinal afferent nerves in flat sheet preparations of the bladder. Guinea pigs with partially obstructed bladders showed a significant increase in conscious voiding frequency compared with sham-operated guinea pigs. Also, nonvoiding contractions increased significantly in both frequency and amplitude. Although spontaneous firing of low-threshold bladder afferents was increased, their stretch-induced firing was reduced. The proportion of capsaicin-sensitive low-threshold afferents increased in obstructed bladders. Interestingly, spontaneous and stretch-induced firing were both significantly increased in high-threshold afferents after obstruction. In summary, sensory signaling increased in the obstructed bladder during the filling phase. This is largely mediated by low-threshold stretch-sensitive afferents that are activated by increased local nonvoiding contractions. Increased spontaneous firing by high-threshold afferents also contributes. Our findings revealed a complex effect of bladder outlet obstruction on different types of bladder afferents that needs consideration for potential therapeutic targeting of lower urinary tract symptoms in obstruction-induced bladder overactivity.

scholarly journals Pharmacological assessment of the contribution of the arterial baroreflex to sympathetic discharge patterns in healthy humans

2018 ◽  
Vol 119 (6) ◽  
pp. 2166-2175 ◽  
Author(s):  
Jacqueline K. Limberg ◽  
Elizabeth P. Ott ◽  
Walter W. Holbein ◽  
Sarah E. Baker ◽  
Timothy B. Curry ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Sympathetic Activity ◽  
High Threshold ◽  
Neural Activation ◽  
Afferent Activity ◽  
Cluster Number ◽  
Arterial Blood ◽  
Rate Coding ◽  
Low Threshold

To study how changes in baroreceptor afferent activity affect patterns of sympathetic neural activation, we manipulated arterial blood pressure with intravenous nitroprusside (NTP) and phenylephrine (PE) and measured action potential (AP) patterns with wavelet-based methodology. We hypothesized that 1) baroreflex unloading (NTP) would increase firing of low-threshold axons and recruitment of latent axons and 2) baroreflex loading (PE) would decrease firing of low-threshold axons. Heart rate (HR, ECG), arterial blood pressure (BP, brachial catheter), and muscle sympathetic nerve activity (MSNA, microneurography of peroneal nerve) were measured at baseline and during steady-state systemic, intravenous NTP (0.5–1.2 µg·kg−1·min−1, n = 13) or PE (0.2–1.0 µg·kg−1·min−1, n = 9) infusion. BP decreased and HR and integrated MSNA increased with NTP ( P < 0.01). AP incidence (326 ± 66 to 579 ± 129 APs/100 heartbeats) and AP content per integrated burst (8 ± 1 to 11 ± 2 APs/burst) increased with NTP ( P < 0.05). The firing probability of low-threshold axons increased with NTP, and recruitment of high-threshold axons was observed (22 ± 3 to 24 ± 3 max cluster number, 9 ± 1 to 11 ± 1 clusters/burst; P < 0.05). BP increased and HR and integrated MSNA decreased with PE ( P < 0.05). PE decreased AP incidence (406 ± 128 to 166 ± 42 APs/100 heartbeats) and resulted in fewer unique clusters (15 ± 2 to 9 ± 1 max cluster number, P < 0.05); components of an integrated burst (APs or clusters per burst) were not altered ( P > 0.05). These data support a hierarchical pattern of sympathetic neural activation during manipulation of baroreceptor afferent activity, with rate coding of active neurons playing the predominant role and recruitment/derecruitment of higher-threshold units occurring with steady-state hypotensive stress. NEW & NOTEWORTHY To study how changes in baroreceptor afferent activity affect patterns of sympathetic neural activation, we manipulated arterial blood pressure with intravenous nitroprusside and phenylephrine and measured sympathetic outflow with wavelet-based methodology. Baroreflex unloading increased sympathetic activity by increasing firing probability of low-threshold axons (rate coding) and recruiting new populations of high-threshold axons. Baroreflex loading decreased sympathetic activity by decreasing the firing probability of larger axons (derecruitment); however, the components of an integrated burst were unaffected.

Calcium currents of cardiovascular neurons isolated from adult guinea pigs

1987 ◽  
Vol 252 (4) ◽  
pp. H867-H871
Author(s):  
D. L. Kunze
Keyword(s):  
Guinea Pigs ◽  
Action Potentials ◽  
Calcium Current ◽  
Threshold Current ◽  
Bipolar Cells ◽  
Calcium Currents ◽  
High Threshold ◽  
Calcium Dependent ◽  
Low Threshold ◽  
Patch Technique

A preparation of cells isolated from the medial and dorsal nuclei of the solitary tract of the medulla of adult guinea pigs was developed to examine the electrical properties of neurons isolated from an area of the central nervous system which is involved in the control of arterial pressure and heart rate. Bipolar cells of approximately 10 microns diameter were obtained on enzymatic dispersion. The cells were studied with the use of the patch technique for whole cell recording. Action potentials were elicited by depolarizing pulses in the presence of 10(-5) M tetrodotoxin which blocked a sodium-dependent current. These action potentials were calcium dependent and were eliminated by adding 1 mM Cd to the bath. In all cells studied, two voltage-dependent components to the calcium current were identified. In 10 mM Ca a high-threshold component activated at approximately -20 mV from holding potentials of -30 mV. A second lower threshold component was activated at -40 mV from more negative holding potentials of -80 mV. The low-threshold component was rapidly inactivating, whereas the high-threshold current slowly inactivated. The peak amplitudes of the two components were similar. Both components were blocked by 1 mM Cd. A role for the low-threshold calcium current in generating repetitive activity is postulated.

scholarly journals MON-015 Pregnancy Adapts Circadian Rhythms in the Reproductive Axis: Impact on Labor Regulating Drug Efficacy

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Hanne Mette Hoffmann ◽  
Thu V Duong ◽  
Duong Nguyen ◽  
Asad Muhammed ◽  
Alexandra M Yaw
Keyword(s):  
Transcription Factors ◽  
Circadian Rhythm ◽  
Circadian Rhythms ◽  
Ex Vivo ◽  
Drug Efficacy ◽  
Time Of Day ◽  
Receptor Expression ◽  
Behavioral Activity ◽  
Reproductive Tissues ◽  
Reproductive Axis

Abstract Molecular and behavioral timekeeping is regulated by the circadian system represented on the cellular level by clock transcription factors, including Period2 (PER2), Bmal1, Clock and Cry. These transcription factors drive a daily ~24h rhythm in gene expression leading to tissue specific receptor expression optimizing sensitivity to hormones and drugs dependent on the time of day. To synchronize circadian rhythms in the body to the time of day, the brain’s suprachiasmatic nucleus (SCN) translates environmental light information into neuronal and endocrine signals allowing circadian rhythm synchrony. Despite the critical role of circadian rhythms in fertility, it remains unknown how circadian rhythms change within reproductive tissues during pregnancy, and how these adaptations might impact drug efficacy. Monitoring wheel-running patterns in circadian PER2::luciferase (PER2::LUC) reporter mice, we confirmed that pregnancy is associated with reductions of activity and identified a correlation between delayed onset of behavioral activity during late pregnancy and ex vivo SCN PER2::LUC period, whereas no correlation between arcuate nucleus PER2::LUC rhythms was identified. The time of day of peak PER2::LUC expression provides a time-stamp as to the circadian phase of a tissue. Pregnancy impacted circadian synchrony in the reproductive axis, with the most dramatic change within the uterus. To understand how circadian rhythms responded to input during pregnancy, we performed a pharmacology study and found that circadian rhythm generation in the uterus responded differentially to hormones regulating pregnancy and labor depending on gestational age and the time of day of drug administration. To test for functional changes in uterine contraction capacity, we recorded ex vivo uterine contractions. Our preliminary data reveal a circadian change in uterine function in the mouse, which impacted labor regulating drug efficacy depending on the time of day. Together our data show that pregnancy is associated with behavioral changes in locomotor activity patterns, as well as adaptations in phase-relationships in reproductive tissues. Our chrono-pharmacology study indicates that a better understanding of labor-regulating drug efficacy can potentially allow increased efficacy of currently used drugs in the clinic to both induce labor as well as halt preterm labor.

Firing patterns and functional roles of different classes of spinal afferents in rectal nerves during colonic migrating motor complexes in mouse colon

2012 ◽  
Vol 303 (3) ◽  
pp. G404-G411 ◽  
Author(s):  
Vladimir P. Zagorodnyuk ◽  
Melinda Kyloh ◽  
Simon J. Brookes ◽  
Sarah J. Nicholas ◽  
Nick J. Spencer
Keyword(s):  
Firing Rate ◽  
Dynamic Range ◽  
Contractile Activity ◽  
Circular Muscle ◽  
Visceral Afferents ◽  
High Threshold ◽  
Wide Dynamic Range ◽  
Low Threshold ◽  
Spinal Afferents ◽  
Circumferential Stretch

The functional role of the different classes of visceral afferents that innervate the large intestine is poorly understood. Recent evidence suggests that low-threshold, wide-dynamic-range rectal afferents play an important role in the detection and transmission of visceral pain induced by noxious colorectal distension in mice. However, it is not clear which classes of spinal afferents are activated during naturally occurring colonic motor patterns or during intense contractions of the gut smooth muscle. We developed an in vitro colorectum preparation to test how the major classes of rectal afferents are activated during spontaneous colonic migrating motor complex (CMMC) or pharmacologically induced contraction. During CMMCs, circular muscle contractions increased firing in low-threshold, wide-dynamic-range muscular afferents and muscular-mucosal afferents, which generated a mean firing rate of 1.53 ± 0.23 Hz ( n = 8) under isotonic conditions and 2.52 ± 0.36 Hz ( n = 17) under isometric conditions. These low-threshold rectal afferents were reliably activated by low levels of circumferential stretch induced by increases in length (1–2 mm) or load (1–3 g). In a small proportion of cases (5 of 34 units), some low-threshold muscular and muscular-mucosal afferents decreased their firing rate during the peak of the CMMC contractions. High-threshold afferents were never activated during spontaneous CMMC contractions or tonic contractions induced by bethanechol (100 μM). High-threshold rectal afferents were only activated by intense levels of circumferential stretch (10–20 g). These results show that, in the rectal nerves of mice, low-threshold, wide-dynamic-range muscular and muscular-mucosal afferents are excited during contraction of the circular muscle that occurs during spontaneous CMMCs. No activation of high-threshold rectal afferents was detected during CMMCs or intense contractile activity in naïve mouse colorectum.

Chronic Estrogen Sensitizes a Subset of Mechanosensitive Afferents Innervating the Uterine Cervix

2005 ◽  
Vol 93 (4) ◽  
pp. 2167-2173 ◽  
Author(s):  
Baogang Liu ◽  
James C. Eisenach ◽  
Chuanyao Tong
Keyword(s):  
Spontaneous Activity ◽  
Uterine Cervix ◽  
Firing Frequency ◽  
High Threshold ◽  
Group 13 ◽  
Ovx Rats ◽  
Afferent Fibers ◽  
Low Threshold ◽  
Group 5 ◽  
Afferent Response

Estrogen increases reflex nocifensive responses to distension of the uterus and the urinary bladder, but estrogen's effects on afferent response to distension of the uterine cervix, the site of obstetric and some gynecologic pain, has not been studied. Here, single fiber recording of hypogastric nerve responses to uterine cervical distension were obtained from ovariectomized (OVX) rats and OVX rats treated with estrogen (ES). Spontaneous activity was greater in the ES group (13 of 24 units; 54%) than in the OVX group (6 of 27 units; 22%). ES differentially altered the response of low- and high-threshold units to distension. For high-threshold units, firing frequency was increased two- to fourfold with 60–100 gm distension in ES compared with OVX groups ( P < 0.05). In contrast, the response of low-threshold units to distension was not altered by ES. About one-half of units tested in each group responded to a temperature increase from 35 to 49°C. A greater proportion of thermosensitive units were also mechanosensitive in the ES group (7 of 8 afferents, 88%) than in the OVX group (5 of 11 afferents, 45%). Acute application of ES in OVX rats failed to evoke or increase distension-induced responses. These data show the polymodal nature of afferent fibers innervating the uterine cervix. Increased spontaneous activity with ES may play a part in remodeling of the cervical tissue, whereas selective sensitization of high-threshold units by ES might underlie increased pain responses to cervical distension. Failure of acute ES treatment to mimic this suggests a genomic effect.

scholarly journals Carbon dioxide fluxes increase from day to night across European streams

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Katrin Attermeyer ◽  
Joan Pere Casas-Ruiz ◽  
Thomas Fuss ◽  
Ada Pastor ◽  
Sophie Cauvy-Fraunié ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Carbon Dioxide Emissions ◽  
Large Scale ◽  
Carbon Dioxide Flux ◽  
Time Of Day ◽  
Night Time ◽  
Carbon Dioxide Fluxes ◽  
Large Scale Assessment ◽  
Air Interface ◽  
Flux Variability

AbstractGlobally, inland waters emit over 2 Pg of carbon per year as carbon dioxide, of which the majority originates from streams and rivers. Despite the global significance of fluvial carbon dioxide emissions, little is known about their diel dynamics. Here we present a large-scale assessment of day- and night-time carbon dioxide fluxes at the water-air interface across 34 European streams. We directly measured fluxes four times between October 2016 and July 2017 using drifting chambers. Median fluxes are 1.4 and 2.1 mmol m−2 h−1 at midday and midnight, respectively, with night fluxes exceeding those during the day by 39%. We attribute diel carbon dioxide flux variability mainly to changes in the water partial pressure of carbon dioxide. However, no consistent drivers could be identified across sites. Our findings highlight widespread day-night changes in fluvial carbon dioxide fluxes and suggest that the time of day greatly influences measured carbon dioxide fluxes across European streams.

Increased ex-vivo colonic generation of PAF induced by diphenylmethane stimulant laxatives in rats, mice, guinea-pigs and rabbits

1993 ◽  
Vol 45 (10) ◽  
pp. 916-918 ◽  
Author(s):  
A. A. Izzo ◽  
N. Mascolo ◽  
G. Autore ◽  
G. Carlo ◽  
F. Capasso
Keyword(s):  
Guinea Pigs ◽  
Ex Vivo

Electrophysiology of neurosecretory cells from the pituitary intermediate lobe

1988 ◽  
Vol 139 (1) ◽  
pp. 317-328
Author(s):  
R. N. McBurney ◽  
S. J. Kehl
Keyword(s):  
Cell Cultures ◽  
Calcium Ion ◽  
Action Potentials ◽  
Neurosecretory Cells ◽  
Secretory Process ◽  
High Threshold ◽  
Pars Intermedia ◽  
Low Threshold ◽  
Stimulus Secretion Coupling ◽  
Ca2 Channels

One of the goals in studying the electrical properties of neurosecretory cells is to relate their electrical activity to the process of secretion. A central question in these studies concerns the role of transmembrane calcium ion flux in the initiation of the secretory event. With regard to the secretory process in pituitary cells, several research groups have addressed this question in vitro using mixed primary anterior pituitary cell cultures or clonal cell lines derived from pituitary tumours. Other workers, including ourselves, have used homogeneous cell cultures derived from the pituitary intermediate lobes of rats to examine the characteristics of voltage-dependent conductances, the contribution of these conductances to action potentials and their role in stimulus-secretion coupling. Pars intermedia (PI) cells often fire spontaneous action potentials whose frequency can be modified by the injection of sustained currents through the recording electrode. In quiescent cells action potentials can also be evoked by the injection of depolarizing current stimuli. At around 20 degrees C these action potentials have a duration of about 5 ms. Although most of the inward current during action potentials is carried by sodium ions, a calcium ion component can be demonstrated under abnormal conditions. Voltage-clamp experiments have revealed that the membrane of these cells contains high-threshold, L-type, Ca2+ channels and low-threshold Ca2+ channels. Since hormone release from PI cells appears not to be dependent on action potential activity but does depend on external calcium ions, it is not clear what role these Ca2+ channels play in stimulus-secretion coupling in cells of the pituitary pars intermedia. One possibility is that the low-threshold Ca2+ channels are more important to the secretory process than the high-threshold channels.

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