Significance of extracellular potassium in central respiratory control studied in the isolated brainstem–spinal cord preparation of the neonatal rat

Okada, Yasumasa; Kuwana, Shun-ichi; Kawai, Akira; Mückenhoff, K.; Scheid, P.

doi:10.1016/j.resp.2004.10.009

Cited by 21 publications

(18 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…, 1995). Inspiratory activity in vitro similar to eupneic activity in vivo reveals strong regulatory dynamics, whereas hypoxic gasping arises as the final stage when the respiratory network is greatly disturbed (Richter, 2003; Okada et al. , 2005).…”

Section: Discussionsupporting

confidence: 74%

“…Another group of experimental evidence suggests that oxygen supplied via the bathing medium by diffusion is sufficient for normal aerobic metabolism in the brainstem preparation (Brockhaus et al, 1993;Völker et al, 1995). Inspiratory activity in vitro similar to eupneic activity in vivo reveals strong regulatory dynamics, whereas hypoxic gasping arises as the final stage when the respiratory network is greatly disturbed (Richter, 2003;Okada et al, 2005). As disputed elsewhere, the particular in vitro rhythm characteristics might be the result of restricted experimental conditions, lower temperature and removal of sensory and central neuronal inputs (Ballanyi et al, 1999;Richter & Spyer, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…For the brainstem preparation, moderate elevation of total [K + ] in the perfusate to 6.2 m m , above the normal in vivo physiological range of 3–4 m m , is justified as this allows maintenance of optimal reactivity of the preparation. As shown recently, [K + ] moderately elevated to 8 m m augmented the functional connectivity between neurons at the VLM and increased chemosensitivity in the brainstem–spinal cord preparation in comparison with a [K + ] of 4 m m (Okada et al. , 2005).…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Early postnatal changes in respiratory activity in rat in vitro and modulatory effects of substance P

Shvarev¹,

Lagercrantz²

2006

Eur J of Neuroscience

View full text Add to dashboard Cite

Developmental changes in the respiratory activity and its modulation by substance P (SP) were studied in the neonatal rat brainstem-spinal cord preparation from the day of birth to day 3 (P0-P3). The respiratory network activity in the ventrolateral medulla was represented by two types of bursts: basic regular bursts with typical decrementing shape and biphasic bursts appearing after augmented biphasic discharges in inspiratory neurons. With advancing postnatal age the respiratory output was considerably modified; the basic rhythm became faster by 20%, whereas the biphasic burst rate, which was originally 15 times slower, declined further by 180% and the C4 burst duration significantly decreased by 20% due to reduced decay time without preceding changes in the central inspiratory drive. SP had an age-dependent excitatory effect on respiratory activity. In the basic rhythm, SP could induce transient rhythm cessations on P0-P2 but not on P3. For the biphasic burst frequency, the sensitivity to SP significantly decreased from P0 to P3, whereas the range of SP-induced changes increased. In both types of bursts, SP prolonged C4 burst duration due to increasing decay time. This effect was three times greater on P3 and did not depend on the central inspiratory drive. Our results suggest that the potency of SP to regulate the respiratory activity elevates during the early postnatal period. The developmental changes in the respiratory activity appear to represent the transient stage in the maturation of rhythm and pattern generation mechanisms facilitating adaptive behavior of a quickly growing organism.

show abstract

Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Early postnatal changes in respiratory activity in rat in vitro and modulatory effects of substance P

Shvarev¹,

Lagercrantz²

2006

Eur J of Neuroscience

View full text Add to dashboard Cite

show abstract

“…On the contrary, we directly stained the preBötC region and conducted large‐scale imaging, and the dye we used, OGB1, appears to preferentially stain astrocytes (Funke et al 2007; Sasaki et al 2011 a ). Recently, Schnell et al (2011) analysed functional coupling between astrocytes and neurons, detected a rhythmic inwardly directed current that was entrained to neuron population discharges in 10% of preBötC astrocytes by whole‐cell patch recording, and attributed the rhythmic current fluctuation to periodic elevations of extracellular potassium that were produced by efflux from rhythmically oscillating neurons and to consequent changes in potassium equilibrium potentials of astrocytes (Brockhaus et al 1993; Okada et al 2005). However, Schnell et al (2011) did not detect periodic calcium rises in astrocytes coupled with neuronal rhythmic activities.…”

Section: Discussionmentioning

confidence: 99%

Preinspiratory calcium rise in putative pre‐Bötzinger complex astrocytes

Okada

Sasaki

Oku

et al. 2012

The Journal of Physiology

Self Cite

View full text Add to dashboard Cite

Key points• Autonomic respiratory rhythm is essential to maintain lives and is generated in the lower brainstem. The ventrolateral medullary region, called the pre-Bötzinger complex (preBötC), is the kernel for respiratory rhythm generation. Despite previous extensive studies focusing on neurons, the mechanism of how respiratory rhythm is generated has not been fully understood.• Here we show that non-neuronal glial cells (a subset of putative astrocytes) in the preBötC are periodically activated preceding inspiratory neuronal activity, periodic activity of putative astrocytes persists during blockade of neuronal activity, and stimulation of astrocytes in the preBötC induces inspiratory neuronal firings.• These findings together with the previous report that blockade of astrocytic metabolism abolishes inspiratory neural output suggest that astrocytes are functionally involved in respiratory rhythm generation.• These results will help us better understand how respiratory rhythm is generated and how respiratory output is disturbed in various pathological conditions. AbstractThe neural inspiratory activity originates from a ventrolateral medullary region called the pre-Bötzinger complex (preBötC), yet the mechanism underlying respiratory rhythmogenesis is not completely understood. Recently, the role of not only neurons but astrocytes in the central respiratory control has attracted considerable attention. Here we report our discovery that an intracellular calcium rise in a subset of putative astrocytes precedes inspiratory neuronal firing in rhythmically active slices. Functional calcium imaging from hundreds of preBötC cells revealed that a subset of putative astrocytes exhibited rhythmic calcium elevations preceding inspiratory neuronal activity with a time lag of approximately 2 s. These preinspiratory putative astrocytes maintained their rhythmic activities even during the blockade of neuronal activity with tetrodotoxin, whereas the rhythm frequency was lowered and the intercellular phases of these rhythms were decoupled. In addition, optogenetic stimulation of preBötC putative astrocytes induced firing of inspiratory neurons. These findings raise the possibility that astrocytes in the preBötC are actively involved in respiratory rhythm generation in rhythmically active slices.

show abstract

“…In preparations with a major amount of rostral tissue, extracellular [K + ] is several millimolar higher in the vicinity of preBötC neurons than in the superfusate, due to the modest K + gradient (Brockhaus et al 1993; Okada et al 2005). These elevated interstitial K + levels may antagonize the depressing action of elevated superfusate Ca 2+ as suggested by the finding that preBötC rhythm persisted in ‘Suzue‐type’ solution after transection of brainstem–spinal cords between the preBötC and VII, but was abolished upon subsequent removal of the transected rostral aspect of the preparation (Onimaru et al 2006).…”

Section: Discussionmentioning

confidence: 99%

Dependence on extracellular Ca²⁺/K⁺ antagonism of inspiratory centre rhythms in slices and en bloc preparations of newborn rat brainstem

Ruangkittisakul¹,

Secchia²,

Bornes³

et al. 2007

The Journal of Physiology

View full text Add to dashboard Cite

The pre-Bötzinger Complex (preBötC) inspiratory centre remains active in isolated brainstem-spinal cords and brainstem slices. The extent to which findings in these models depend on their dimensions or superfusate [K + ] and [Ca 2+ ] (both of which determine neuronal excitability) is not clear. We report here that inspiratory-related rhythms in newborn rat slices and brainstem-spinal cords with defined boundaries were basically similar in physiological Ca 2+ (1.2 mM) and K + (3 mM). Hypoglossal nerve rhythm was 1 : 1-coupled to preBötC activity in slices and to cervical nerve bursts in en bloc preparations lacking the facial motonucleus (VII). Hypoglossal rhythm was depressed in brainstems containing (portions of) VII, while pre/postinspiratory lumbar nerve bursting was present only in preparations with > 79% VII. preBötC-related slice rhythms were inhibited in 1.5 mM Ca 2+ solution, whereas their longevity and burst rate were substantially augmented in 1 mM Ca 2+ . Ca 2+ depression of slice rhythms was antagonized by raising superfusate K + to 8-10 mM. This strong extracellular Ca 2+ /K + antagonism of inspiratory (motor) rhythms was also revealed in brainstem-spinal cords without VII, while the inhibition was progressively attenuated with increasing amount of rostral tissue. We hypothesize that depression of hypoglossal rhythm and decreased Ca 2+ sensitivity of preBötC rhythm are probably not related to an increased content of rostral respiratory structures, but rather to larger brainstem dimensions resulting in interstitial gradients for neuromodulator(s) and K + , respectively. We discuss whether block of pre/postinspiratory activity in preparations with < 79% VII is due to impairment of the pathway from preinspiratory interneurons to abdominal muscles

show abstract

Significance of extracellular potassium in central respiratory control studied in the isolated brainstem–spinal cord preparation of the neonatal rat

Cited by 21 publications

References 31 publications

Early postnatal changes in respiratory activity in rat in vitro and modulatory effects of substance P

Early postnatal changes in respiratory activity in rat in vitro and modulatory effects of substance P

Preinspiratory calcium rise in putative pre‐Bötzinger complex astrocytes

Dependence on extracellular Ca²⁺/K⁺ antagonism of inspiratory centre rhythms in slices and en bloc preparations of newborn rat brainstem

Contact Info

Product

Resources

About

Significance of extracellular potassium in central respiratory control studied in the isolated brainstem–spinal cord preparation of the neonatal rat

Cited by 21 publications

References 31 publications

Early postnatal changes in respiratory activity in rat in vitro and modulatory effects of substance P

Early postnatal changes in respiratory activity in rat in vitro and modulatory effects of substance P

Preinspiratory calcium rise in putative pre‐Bötzinger complex astrocytes

Dependence on extracellular Ca2+/K+ antagonism of inspiratory centre rhythms in slices and en bloc preparations of newborn rat brainstem

Contact Info

Product

Resources

About

Dependence on extracellular Ca²⁺/K⁺ antagonism of inspiratory centre rhythms in slices and en bloc preparations of newborn rat brainstem