Perinatal inflammation and gestational intermittent hypoxia disturbs respiratory rhythm generation and long-term facilitation in vitro: partial protection by acute minocycline

The role of pacemaker properties in vertebrate respiratory rhythm generation is not well understood. To address this question from a comparative perspective, brain stems from adult turtles were isolated in vitro, and respiratory motor bursts were recorded on hypoglossal (XII) nerve rootlets. The goal was to test whether burst frequency could be altered by conditions known to alter respiratory pacemaker neuron activity in mammals (e.g., increased bath KCl or blockade of specific inward currents). While bathed in artificial cerebrospinal fluid (aCSF), respiratory burst frequency was not correlated with changes in bath KCl (0.5–10.0 mM). Riluzole (50 μM; persistent Na+ channel blocker) increased burst frequency by 31 ± 5% ( P < 0.05) and decreased burst amplitude by 42 ± 4% ( P < 0.05). In contrast, flufenamic acid (FFA, 20–500 μM; Ca2+-activated cation channel blocker) reduced and abolished burst frequency in a dose- and time-dependent manner ( P < 0.05). During synaptic inhibition blockade with bicuculline (50 μM; GABAA channel blocker) and strychnine (50 μM; glycine receptor blocker), rhythmic motor activity persisted, and burst frequency was directly correlated with extracellular KCl (0.5–10.0 mM; P = 0.005). During synaptic inhibition blockade, riluzole (50 μM) did not alter burst frequency, whereas FFA (100 μM) abolished burst frequency ( P < 0.05). These data are most consistent with the hypothesis that turtle respiratory rhythm generation requires Ca2+-activated cation channels but not pacemaker neurons, which thereby favors the group-pacemaker model. During synaptic inhibition blockade, however, the rhythm generator appears to be transformed into a pacemaker-driven network that requires Ca2+-activated cation channels.

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2P392 Two modes of respiratory rhythm generation in the newborn rat brainstem-spinal cord preparation in vitro(44. Neuro-biophysics,Poster Session,Abstract,Meeting Program of EABS & BSJ 2006)

Seibutsu Butsuri ◽

10.2142/biophys.46.s393_4 ◽

2006 ◽

Vol 46 (supplement2) ◽

pp. S393

Author(s):

Hiroshi Onimaru

Keyword(s):

Spinal Cord ◽

Poster Session ◽

Respiratory Rhythm ◽

Rhythm Generation ◽

Newborn Rat ◽

Meeting Program ◽

Respiratory Rhythm Generation ◽

Rat Brainstem

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TASK Channels Contribute to the K+-Dominated Leak Current Regulating Respiratory Rhythm Generation In Vitro

Journal of Neuroscience ◽

10.1523/jneurosci.4017-09.2010 ◽

2010 ◽

Vol 30 (12) ◽

pp. 4273-4284 ◽

Cited By ~ 47

Author(s):

H. Koizumi ◽

S. E. Smerin ◽

T. Yamanishi ◽

B. R. Moorjani ◽

R. Zhang ◽

...

Keyword(s):

Respiratory Rhythm ◽

Rhythm Generation ◽

Leak Current ◽

Task Channels ◽

Respiratory Rhythm Generation

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Spontaneous respiratory rhythm generation in in vitro upper cervical slice preparations of neonatal mice

The Journal of Physiological Sciences ◽

10.1007/s12576-010-0091-1 ◽

2010 ◽

Vol 60 (4) ◽

pp. 303-307 ◽

Cited By ~ 7

Author(s):

Suguru Kobayashi ◽

Yutaka Fujito ◽

Kiyoji Matsuyama ◽

Mamoru Aoki

Keyword(s):

Respiratory Rhythm ◽

Rhythm Generation ◽

Neonatal Mice ◽

Upper Cervical ◽

Respiratory Rhythm Generation

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Time-dependent modulation of carotid body afferent activity during and after intermittent hypoxia

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00788.2004 ◽

2005 ◽

Vol 288 (6) ◽

pp. R1571-R1580 ◽

Cited By ~ 31

Author(s):

Kevin J. Cummings ◽

Richard J. A. Wilson

Keyword(s):

Carotid Body ◽

Intermittent Hypoxia ◽

Current Data ◽

Time Dependent ◽

Severe Hypoxia ◽

Afferent Activity ◽

Direct Role ◽

Long Term Facilitation

The ventilatory response to several minutes of hypoxia consists of various time-dependent phenomena, some of which occur during hypoxia (e.g., short-term depression), whereas others appear on return to normoxia (e.g., posthypoxic frequency decline). Additional phenomena can be elicited by acute, intermittent hypoxia (e.g., progressive augmentation, long-term facilitation). Current data suggest that these phenomena originate centrally. We tested the hypothesis that carotid body afferent activity undergoes time-dependent modulation, consistent with a direct role in these ventilatory phenomena. Using an in vitro rat carotid body preparation, we found that 1) afferent activity declined during the first 5 min of severe (40 Torr Po2), moderate (60 Torr Po2), or mild (80 Torr Po2) hypoxia; 2) after return to normoxia (100 Torr Po2) and after several minutes of moderate or severe hypoxia, afferent activity was transiently reduced compared with prehypoxic levels; and 3) with successive 5-min bouts of mild, moderate, or severe hypoxia, afferent activity during bouts increased progressively. We call these phenomena sensory hypoxic decline, sensory posthypoxic decline, and sensory progressive augmentation, respectively. These phenomena were stimulus specific: similar phenomena were not seen with 5-min bouts of normoxic hypercapnia (100 Torr Po2 and 50–60 Torr Pco2) or hypoxic hypocapnia (60 Torr Po2 and 30 Torr Pco2). However, bouts of either normoxic hypercapnia or hypocapnic hypoxia resulted in sensory long-term facilitation. We suggest time-dependent carotid body activity acts in parallel with central mechanisms to shape the dynamics of ventilatory responses to respiratory chemostimuli.

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