A1 Adenosine Receptors Modulate Respiratory Activity of the Neonatal Mouse Via the cAMP-Mediated Signaling Pathway

• Published in: Journal of neurophysiology Vol. 81; no. 1; pp. 247 - 255
• Main Authors: Mironov, S. L, Langohr, K, Richter, D. W
• Format: Journal Article
• Language: English
• Published: United States Am Phys Soc 01.01.1999
• Subjects: Adenosine Triphosphate - physiology; Animals; Animals, Newborn - physiology; Cyclic AMP - physiology; Electric Stimulation; Electrophysiology; Female; In Vitro Techniques; Male; Membrane Potentials - drug effects; Membrane Potentials - physiology; Mice; Patch-Clamp Techniques; Potassium Channels - metabolism; Purinergic P1 Receptor Agonists; Purinergic P1 Receptor Antagonists; Receptors, Purinergic P1 - physiology; Respiratory Mechanics - drug effects; Respiratory Mechanics - physiology; Signal Transduction - drug effects; Signal Transduction - physiology
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.1999.81.1.247

S. L. Mironov , K. Langohr , and D. W. Richter II Department of Physiology, University of Göttingen, 37073 Göttingen, Germany Mironov, S. L., K. Langohr, and D. W. Richter. A 1 adenosine receptors modulate respiratory activity of the neonatal mouse via the cAMP-mediated signaling pathway. J. Neurophysiol. 81: 247-255, 1999. The effects of adenosine and its analogs on the function of the respiratory center were studied in the spontaneously active rhythmic slice of neonatal and juvenile mice (4-14 days old). Whole cell, spontaneous postsynaptic currents (sPSCs) and single channel K ATP currents were recorded in inspiratory neurons of the pre-Bötzinger complex. Adenosine (50-600 µM) inhibited the respiratory rhythm. This was accompanied by increase in the activity of K ATP channels in cell-attached patches. The A 1 adenosine receptor agonist, 2-chloro-N 6 -cyclopentyladenosine (CCPA, 0.3-2 µM), inhibited the respiratory rhythm, sPSCs, and enhanced activity of K ATP channels. The A 1 adenosine receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 1-3 µM), showed opposite effects and occluded the CCPA actions. Agents specific for A 2 adenosine receptors (CGS 21860 and NECA, both applied at 1-10 µM) were without effect. Elevation of intracellular cAMP concentration ([cAMP] i ) by 8-Br-cAMP (200-500 µM), forskolin (0.5-2 µM), or isobutylmethylxantine (IBMX, 30-90 µM) reinforced the rhythm, whereas NaF (100-800 µM) depressed it. The open probability of single K ATP channels in cell-attached patches decreased after application of forskolin and increased in the presence of NaF. [cAMP] i elevation reversed the effects of A 1 receptors both on the respiratory rhythm and K ATP channels. A 1 receptors and [cAMP] i modified the hypoxic respiratory response. In the presence of A 1 agonists the duration of hypoxic augmentation shortened, and depression of the respiratory rhythm occurred earlier. Elevation of [cAMP] i prolonged augmentation and delayed the development of the depression. We conclude that A 1 adenosine receptors modulate the respiratory rhythm via inhibition of intracellular cAMP production and concomitant activation of K ATP channels.