Limits...
β-Noradrenergic receptor activation specifically modulates the generation of sighs in vivo and in vitro.

Viemari JC, Garcia AJ, Doi A, Elsen G, Ramirez JM - Front Neural Circuits (2013)

Bottom Line: By contrast, all parameters of bursting pacemakers that rely on the non-specific cation current (I(CAN)) remained unaffected.Moreover, riluzole, which blocks bursting in I(Nap) pacemakers abolished sighs altogether, while flufenamic acid (FFA) which blocks the I(CAN) current did not alter the sigh-increasing effect caused by β-NR.Our results suggest that the selective β-NR action of sighs may result from the modulation of I(Nap) pacemaker activity and that disturbances in noradrenergic system may contribute to abnormal arousal response.

View Article: PubMed Central - PubMed

Affiliation: Team P3M, Institut de Neurosciences de la Timone, UMR 7289, CNRS, Aix Marseille Univesité , Marseille, France.

ABSTRACT
The pre-Bötzinger complex (preBötC), an area that is critical for generating breathing (eupnea), gasps and sighs is continuously modulated by catecholamines. These amines and the generation of sighs have also been implicated in the regulation of arousal. Here we studied the catecholaminergic modulation of sighs not only in anesthetized freely breathing mice (in vivo), but also in medullary slice preparations that contain the preBötC and that generate fictive eupneic and sigh rhythms in vitro. We demonstrate that activating β-noradrenergic receptors (β-NR) specifically increases the frequency of sighs, while eupnea remains unaffected both in vitro and in vivo. β-NR activation specifically increased the frequency of intrinsically bursting pacemaker neurons that rely on persistent sodium current (I(Nap)). By contrast, all parameters of bursting pacemakers that rely on the non-specific cation current (I(CAN)) remained unaffected. Moreover, riluzole, which blocks bursting in I(Nap) pacemakers abolished sighs altogether, while flufenamic acid (FFA) which blocks the I(CAN) current did not alter the sigh-increasing effect caused by β-NR. Our results suggest that the selective β-NR action of sighs may result from the modulation of I(Nap) pacemaker activity and that disturbances in noradrenergic system may contribute to abnormal arousal response. The β-NR action on the preBötC may be an important mechanism in modulating behaviors that are specifically associated with sighs, such as the regulation of the early events leading to the arousal response.

Show MeSH

Related in: MedlinePlus

Blockade of the INap blocks the β-noradrenergic modulation of sigh activity. (A1) ∫VRG activity recorded from a slice under control conditions. (A2) Application of riluzole (20 μM) abolished the generation of sigh activity. (A3) Riluzole did prevent the effects of NE on the frequency of sigh activity. (B1) ∫VRG activity recorded from a slice under control conditions. (B2) Application of riluzole (20 μM) abolished the generation of sigh activity. (B3) Riluzole did block the effect of isoproterenol (20 μM) on fictive sigh activity.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3824105&req=5

Figure 9: Blockade of the INap blocks the β-noradrenergic modulation of sigh activity. (A1) ∫VRG activity recorded from a slice under control conditions. (A2) Application of riluzole (20 μM) abolished the generation of sigh activity. (A3) Riluzole did prevent the effects of NE on the frequency of sigh activity. (B1) ∫VRG activity recorded from a slice under control conditions. (B2) Application of riluzole (20 μM) abolished the generation of sigh activity. (B3) Riluzole did block the effect of isoproterenol (20 μM) on fictive sigh activity.

Mentions: To explore the potential involvement of INap in the generation of spontaneous sigh activity, we applied riluzole at concentrations that also block bursting in INap-dependent pacemaker neurons as previously described (Del Negro et al., 2002, 2005; Peña et al., 2004; Viemari and Ramirez, 2006). Riluzole (20 μM) alone abolished fictive sigh activity, but the fictive eupneic activity persisted (Figures 9A,B). Subsequent application of NE (20 μM, n = 6, Figure 9A3) did not induce sigh activity and after 5 min the rhythm completely disintegrated as previously reported (Viemari and Ramirez, 2006). We performed the same set of experiments replacing NE with isoproterenol, the β-NR agonist, after riluzole and the sigh activity never came back (Figure 9B3, n = 5) which support our hypothesis that INap mechanisms are important for the modulation of sigh activity.


β-Noradrenergic receptor activation specifically modulates the generation of sighs in vivo and in vitro.

Viemari JC, Garcia AJ, Doi A, Elsen G, Ramirez JM - Front Neural Circuits (2013)

Blockade of the INap blocks the β-noradrenergic modulation of sigh activity. (A1) ∫VRG activity recorded from a slice under control conditions. (A2) Application of riluzole (20 μM) abolished the generation of sigh activity. (A3) Riluzole did prevent the effects of NE on the frequency of sigh activity. (B1) ∫VRG activity recorded from a slice under control conditions. (B2) Application of riluzole (20 μM) abolished the generation of sigh activity. (B3) Riluzole did block the effect of isoproterenol (20 μM) on fictive sigh activity.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3824105&req=5

Figure 9: Blockade of the INap blocks the β-noradrenergic modulation of sigh activity. (A1) ∫VRG activity recorded from a slice under control conditions. (A2) Application of riluzole (20 μM) abolished the generation of sigh activity. (A3) Riluzole did prevent the effects of NE on the frequency of sigh activity. (B1) ∫VRG activity recorded from a slice under control conditions. (B2) Application of riluzole (20 μM) abolished the generation of sigh activity. (B3) Riluzole did block the effect of isoproterenol (20 μM) on fictive sigh activity.
Mentions: To explore the potential involvement of INap in the generation of spontaneous sigh activity, we applied riluzole at concentrations that also block bursting in INap-dependent pacemaker neurons as previously described (Del Negro et al., 2002, 2005; Peña et al., 2004; Viemari and Ramirez, 2006). Riluzole (20 μM) alone abolished fictive sigh activity, but the fictive eupneic activity persisted (Figures 9A,B). Subsequent application of NE (20 μM, n = 6, Figure 9A3) did not induce sigh activity and after 5 min the rhythm completely disintegrated as previously reported (Viemari and Ramirez, 2006). We performed the same set of experiments replacing NE with isoproterenol, the β-NR agonist, after riluzole and the sigh activity never came back (Figure 9B3, n = 5) which support our hypothesis that INap mechanisms are important for the modulation of sigh activity.

Bottom Line: By contrast, all parameters of bursting pacemakers that rely on the non-specific cation current (I(CAN)) remained unaffected.Moreover, riluzole, which blocks bursting in I(Nap) pacemakers abolished sighs altogether, while flufenamic acid (FFA) which blocks the I(CAN) current did not alter the sigh-increasing effect caused by β-NR.Our results suggest that the selective β-NR action of sighs may result from the modulation of I(Nap) pacemaker activity and that disturbances in noradrenergic system may contribute to abnormal arousal response.

View Article: PubMed Central - PubMed

Affiliation: Team P3M, Institut de Neurosciences de la Timone, UMR 7289, CNRS, Aix Marseille Univesité , Marseille, France.

ABSTRACT
The pre-Bötzinger complex (preBötC), an area that is critical for generating breathing (eupnea), gasps and sighs is continuously modulated by catecholamines. These amines and the generation of sighs have also been implicated in the regulation of arousal. Here we studied the catecholaminergic modulation of sighs not only in anesthetized freely breathing mice (in vivo), but also in medullary slice preparations that contain the preBötC and that generate fictive eupneic and sigh rhythms in vitro. We demonstrate that activating β-noradrenergic receptors (β-NR) specifically increases the frequency of sighs, while eupnea remains unaffected both in vitro and in vivo. β-NR activation specifically increased the frequency of intrinsically bursting pacemaker neurons that rely on persistent sodium current (I(Nap)). By contrast, all parameters of bursting pacemakers that rely on the non-specific cation current (I(CAN)) remained unaffected. Moreover, riluzole, which blocks bursting in I(Nap) pacemakers abolished sighs altogether, while flufenamic acid (FFA) which blocks the I(CAN) current did not alter the sigh-increasing effect caused by β-NR. Our results suggest that the selective β-NR action of sighs may result from the modulation of I(Nap) pacemaker activity and that disturbances in noradrenergic system may contribute to abnormal arousal response. The β-NR action on the preBötC may be an important mechanism in modulating behaviors that are specifically associated with sighs, such as the regulation of the early events leading to the arousal response.

Show MeSH
Related in: MedlinePlus