Adenosine-induced inhibition of vagal motoneuron excitability: receptor subtype and mechanisms.
With the use of intracellular techniques and a medullary slice preparation, we examined the changes in cellular and membrane properties of single adult rat vagal motoneurons during exposure to potent and specific agonists and antagonists of adenosine A1 and A2 receptors. A1 receptor stimulation increased input resistance, but markedly reduced spontaneous neuronal firing and increased rheobase. A1 agonists also increased the amplitude of the action potential afterhyperpolarization (AHP) in a dose-dependent manner. Prior treatment with A1 antagonists blocked these electrophysiological effects. Blockade of Ca2+ entry with Co2+ abolished the AHP increase. Synaptic blockade with both tetrodotoxin and high Mg2+, low Ca2+ solutions prevented the increase in input resistance. A2 receptor stimulation was without effect. Perfusion with adenosine in the presence of dipyridamole caused effects similar to A1 agonist stimulation, but no effect in the absence of dipyridamole. These results show that adenosine decreases vagal motoneuron excitability by stimulating A1 receptors. Our data also support the idea that the adenosine-induced decrease in excitability is presynaptic in nature. In addition, the AHP increase may be mediated by enhanced Ca2+ entry into the postsynaptic neuron.
Marks
J D
JD
Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut 06510.
Donnelly
D F
DF
Haddad
G G
GG
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D004594:Electrophysiology; D066298:In Vitro Techniques; D008526:Medulla Oblongata / Q000502:physiology; D009046:Motor Neurons / Q000187:drug effects* / Q000502:physiology; D009433:Neural Inhibition; D051381:Rats; D011983:Receptors, Purinergic / Q000145:classification / Q000502:physiology*; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission; D014630:Vagus Nerve / Q000166:cytology / Q000187:drug effects* / Q000502:physiology
D011983:Receptors, Purinergic; D000241:Adenosine