Adenosinergic modulation of neuronal activity in the pond snail Lymnaea stagnalis

Abstract

SUMMARY 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 (A1R). Action potential (AP) frequency and membrane potential (Vm) 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 Vm. The A1R agonist cyclopentyladenosine (CPA) mimicked the results obtained with adenosine whereas antagonism of the A1R with 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) had no effect on AP frequency or Vm but prevented the adenosine and CPA-mediated decreases in neuronal activity. Furthermore, Ca2+ measurements with fluo-4 revealed that A1R activation led to a 12% increase in intracellular Ca2+ 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 Ca2+ levels.