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Modulation of the cough reflex by GABA(A) receptors in the caudal ventral respiratory group of the rabbit.

Cinelli E, Bongianni F, Pantaleo T, Mutolo D - Front Physiol (2012)

Bottom Line: Bicuculline (1 mM) increased peak abdominal activity and respiratory frequency due to decreases in T(E).On the contrary, muscimol (0.3 mM) abolished abdominal activity and decreased respiratory frequency due to increases in T(E).However, the number and intensity of expiratory thrusts were enhanced by bicuculline and suppressed by muscimol.

View Article: PubMed Central - PubMed

Affiliation: Dipartimento di Scienze Fisiologiche, Università degli Studi di Firenze Firenze, Italy.

ABSTRACT
We have previously shown that the caudal ventral respiratory group (cVRG) is a possible site of action of some antitussive drugs and plays a crucial role in determining both the expiratory and inspiratory components of the cough motor pattern. In addition, it has been reported that medullary expiratory neurons of the cVRG are subject to potent GABAergic gain modulation. This study was devoted to investigate the role of cVRG GABA(A) receptors in the control of baseline respiratory activity and cough responses to mechanical and chemical (citric acid) stimulation of the tracheobronchial tree. To this purpose, bilateral microinjections (30-50 nl) of bicuculline or muscimol were performed into the cVRG of pentobarbital sodium-anesthetized, spontaneously breathing rabbits. Bicuculline (1 mM) increased peak abdominal activity and respiratory frequency due to decreases in T(E). Cough responses were potentiated mainly owing to increases in the cough number. The recovery was observed within ~2 h. On the contrary, muscimol (0.3 mM) abolished abdominal activity and decreased respiratory frequency due to increases in T(E). In addition, cough responses were progressively reduced and completely suppressed within ~20 min. Partial recovery of cough responses was achieved after ~3 h or within ~5 min following bicuculline microinjections at the same locations. The sneeze reflex induced by mechanical stimulation of the nasal mucosa persisted following bicuculline and muscimol microinjections. However, the number and intensity of expiratory thrusts were enhanced by bicuculline and suppressed by muscimol. The results provide evidence that a potent GABA(A)-mediated inhibitory modulation is exerted at the level of the cVRG not only on respiratory activity, but also on cough and sneeze reflex responses.

No MeSH data available.


Related in: MedlinePlus

Potentiating effects on the cough reflex and on the sneeze reflex ~10 min after bilateral microinjections of bicuculline into the cVRG of one anesthetized spontaneously breathing rabbit. Stimulation periods marked by filled bars. Phr IN, phrenic integrated neurogram; Phr N, phrenic neurogram; Abd IEMG, abdominal integrated electromyographic activity; Abd EMG, abdominal electromyographic activity.
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Figure 2: Potentiating effects on the cough reflex and on the sneeze reflex ~10 min after bilateral microinjections of bicuculline into the cVRG of one anesthetized spontaneously breathing rabbit. Stimulation periods marked by filled bars. Phr IN, phrenic integrated neurogram; Phr N, phrenic neurogram; Abd IEMG, abdominal integrated electromyographic activity; Abd EMG, abdominal electromyographic activity.

Mentions: Bilateral microinjections (n = 5) of 1 mM bicuculline (30–50 nl; 30–50 pmol) at the selected sites of the cVRG increased peak abdominal activity and respiratory frequency (from 51.2 ± 2.6 to 100.2 ± 9.5 breaths min−1; P < 0.005) due to decreases in TE (Table 1). Changes in respiratory activity developed progressively and reached their maximum within ~10 min, while recovery occurred within ~2 h. No significant changes in arterial blood pressure were observed (Table 1). End-tidal CO2 partial pressure decreased from 27.07 ± 0.72 to 22.54 ± 0.81 mmHg (P < 0.05). Changes in cough-related variables 10 min after bilateral microinjections of 1 mM bicuculline are reported in Table 2. Cough responses caused by mechanical stimulation of the tracheobronchial tree displayed increases in the cough number, while cough responses induced by citric acid inhalation displayed increases both in the cough number and peak abdominal activity associated with decreases in the cough-related TT due to reductions in both TI and TE (Table 2 and Figure 2). Bicuculline microinjections also caused concomitant changes in sneeze-related variables. Increases in the number of the expiratory thrusts and in peak abdominal activity, without significant changes in peak phrenic activity were observed (Table 3 and Figure 2). The recovery of both cough and sneeze responses was obtained within ~2 h.


Modulation of the cough reflex by GABA(A) receptors in the caudal ventral respiratory group of the rabbit.

Cinelli E, Bongianni F, Pantaleo T, Mutolo D - Front Physiol (2012)

Potentiating effects on the cough reflex and on the sneeze reflex ~10 min after bilateral microinjections of bicuculline into the cVRG of one anesthetized spontaneously breathing rabbit. Stimulation periods marked by filled bars. Phr IN, phrenic integrated neurogram; Phr N, phrenic neurogram; Abd IEMG, abdominal integrated electromyographic activity; Abd EMG, abdominal electromyographic activity.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3475209&req=5

Figure 2: Potentiating effects on the cough reflex and on the sneeze reflex ~10 min after bilateral microinjections of bicuculline into the cVRG of one anesthetized spontaneously breathing rabbit. Stimulation periods marked by filled bars. Phr IN, phrenic integrated neurogram; Phr N, phrenic neurogram; Abd IEMG, abdominal integrated electromyographic activity; Abd EMG, abdominal electromyographic activity.
Mentions: Bilateral microinjections (n = 5) of 1 mM bicuculline (30–50 nl; 30–50 pmol) at the selected sites of the cVRG increased peak abdominal activity and respiratory frequency (from 51.2 ± 2.6 to 100.2 ± 9.5 breaths min−1; P < 0.005) due to decreases in TE (Table 1). Changes in respiratory activity developed progressively and reached their maximum within ~10 min, while recovery occurred within ~2 h. No significant changes in arterial blood pressure were observed (Table 1). End-tidal CO2 partial pressure decreased from 27.07 ± 0.72 to 22.54 ± 0.81 mmHg (P < 0.05). Changes in cough-related variables 10 min after bilateral microinjections of 1 mM bicuculline are reported in Table 2. Cough responses caused by mechanical stimulation of the tracheobronchial tree displayed increases in the cough number, while cough responses induced by citric acid inhalation displayed increases both in the cough number and peak abdominal activity associated with decreases in the cough-related TT due to reductions in both TI and TE (Table 2 and Figure 2). Bicuculline microinjections also caused concomitant changes in sneeze-related variables. Increases in the number of the expiratory thrusts and in peak abdominal activity, without significant changes in peak phrenic activity were observed (Table 3 and Figure 2). The recovery of both cough and sneeze responses was obtained within ~2 h.

Bottom Line: Bicuculline (1 mM) increased peak abdominal activity and respiratory frequency due to decreases in T(E).On the contrary, muscimol (0.3 mM) abolished abdominal activity and decreased respiratory frequency due to increases in T(E).However, the number and intensity of expiratory thrusts were enhanced by bicuculline and suppressed by muscimol.

View Article: PubMed Central - PubMed

Affiliation: Dipartimento di Scienze Fisiologiche, Università degli Studi di Firenze Firenze, Italy.

ABSTRACT
We have previously shown that the caudal ventral respiratory group (cVRG) is a possible site of action of some antitussive drugs and plays a crucial role in determining both the expiratory and inspiratory components of the cough motor pattern. In addition, it has been reported that medullary expiratory neurons of the cVRG are subject to potent GABAergic gain modulation. This study was devoted to investigate the role of cVRG GABA(A) receptors in the control of baseline respiratory activity and cough responses to mechanical and chemical (citric acid) stimulation of the tracheobronchial tree. To this purpose, bilateral microinjections (30-50 nl) of bicuculline or muscimol were performed into the cVRG of pentobarbital sodium-anesthetized, spontaneously breathing rabbits. Bicuculline (1 mM) increased peak abdominal activity and respiratory frequency due to decreases in T(E). Cough responses were potentiated mainly owing to increases in the cough number. The recovery was observed within ~2 h. On the contrary, muscimol (0.3 mM) abolished abdominal activity and decreased respiratory frequency due to increases in T(E). In addition, cough responses were progressively reduced and completely suppressed within ~20 min. Partial recovery of cough responses was achieved after ~3 h or within ~5 min following bicuculline microinjections at the same locations. The sneeze reflex induced by mechanical stimulation of the nasal mucosa persisted following bicuculline and muscimol microinjections. However, the number and intensity of expiratory thrusts were enhanced by bicuculline and suppressed by muscimol. The results provide evidence that a potent GABA(A)-mediated inhibitory modulation is exerted at the level of the cVRG not only on respiratory activity, but also on cough and sneeze reflex responses.

No MeSH data available.


Related in: MedlinePlus