Adenosinergic modulation of neuronal activity in the pond snail Lymnaea stagnalis

Adenosine has been termed a retaliatory metabolite and its neuroprotective effects have been implicated in the hypoxia tolerance of several species; however, its role in the invertebrate CNS remains unclear. To determine if adenosine modulates neuronal activity in invertebrate neurons, we conducted whole-cell recordings from neurons in the central ring ganglia of the anoxia-tolerant pond snail Lymnaea stagnalis during exposure to adenosine and pharmacological compounds known to modulate the type I subclass of adenosine receptors (A(1)R). Action potential (AP) frequency and membrane potential (V(m)) were unchanged under control conditions, and addition of adenosine decreased AP frequency by 47% (from 1.08+/-0.22 to 0.57+/-0.14 Hz) and caused significant hyperpolarization of V(m). The A(1)R agonist cyclopentyladenosine (CPA) mimicked the results obtained with adenosine whereas antagonism of the A(1)R with 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) had no effect on AP frequency or V(m) but prevented the adenosine and CPA-mediated decreases in neuronal activity. Furthermore, Ca(2+) measurements with fluo-4 revealed that A(1)R activation led to a 12% increase in intracellular Ca(2+) concentration and this elevation was also antagonized by DPCPX. Our results suggest that adenosine acting via the adenosine receptor (type I subclass) depresses neuronal activity in the adult L. stagnalis CNS and this depression is correlated with an increase in cytosolic Ca(2+) levels.