The Journal of Neurophysiology Vol. 81 No. 1 January 1999, pp. 247-255
Copyright ©1999 The American Physiological Society

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

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. A₁ 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 A₁ adenosine receptor agonist, 2-chloro-N⁶-cyclopentyladenosine (CCPA, 0.3-2 µM), inhibited the respiratory rhythm, sPSCs, and enhanced activity of K_ATP channels. The A₁ adenosine receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 1-3 µM), showed opposite effects and occluded the CCPA actions. Agents specific for A₂ 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 A₁ receptors both on the respiratory rhythm and K_ATP channels. A₁ receptors and [cAMP]_i modified the hypoxic respiratory response. In the presence of A₁ 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 A₁ adenosine receptors modulate the respiratory rhythm via inhibition of intracellular cAMP production and concomitant activation of K_ATP channels.

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