Ionic mechanism of action of adenosine on the rat superior cervical ganglion.

1. The ionic mechanism responsible for hyperpolarization of the rat superior cervical ganglion (SCG) and depression of the depolarizing response to muscarine by adenosine was studied using an extracellular grease-gap recording technique. 2. Both the hyperpolarizations to adenosine and 2-chloroadenosine and the depression of the response to muscarine by adenosine were potentiated in reduced external calcium (Ca2+). Hyperpolarizations to adenosine were either unaltered or potentiated in the presence of the dihydropyridine Ca2+ channel antagonists, nitrendipine or (+)PN200 110 respectively. Hyperpolarizations to adenosine were unaltered by inorganic Ca2+ channel antagonists except for cobalt, which also antagonized hyperpolarizations to carbachol and depolarizations to muscarine. 3. Hyperpolarizations to adenosine were unaltered in nominally magnesium (Mg2+)-free or in reduced external chloride (Cl-) media. When sodium ions (Na+) were replaced by lithium ions (Li+) maximal responses to adenosine were initially enhanced, returning to pretreatment levels and subsequently reduced in their duration. In contrast, responses to adenosine were significantly enhanced in nominally potassium (K+)-free medium and reduced upon doubling the extracellular K+. 4. Hyperpolarizations were enhanced in the presence of the K+ channel antagonists, 4-aminopyridine and 3,4-diaminopyridine, and reduced by a low concentration (2 mM) of tetraethylammonium (TEA), but not in 10 mM TEA. 5. The results support the hypothesis that adenosine-mediated hyperpolarization of postganglionic neurones of the rat SCG is by a Ca(2+)-independent mechanism and is probably mediated via an increase of a K+ current. The results also indicate that adenosine-induced hyperpolarizations of the rat SCG are independent of the presence of extracellular magnesium.