We tested the effect of anoxia, a "mimic" turtle artificial cerebrospinal fluid (aCSF) consisting of high Ca²⁺ and Mg²⁺ concentrations and low pH and adenosine perfusions, on whole cell conductance (G_w) in turtle brain slices using a whole cell voltage-clamp technique. With EGTA in the recording electrode, anoxic or adenosine perfusions did not change G_w significantly (values range between 2.15 ± 0.24 and 3.24 ± 0.56 nS). However, perfusion with normoxic or anoxic mimic aCSF significantly decreased G_w. High [Ca²⁺] (4.0 or 7.8 mM) perfusions alone could reproduce the changes in G_w found with the mimic perfusions. With the removal of EGTA from the recording electrode, G_w decreased significantly during both anoxic and adenosine perfusions. The A₁-receptor agonist N⁶-cyclopentyladenosine reduced G_w in a dose-dependent manner, whereas the A₁-receptor specific antagonist 8-cyclopentyl-1,3-dipropylxanthine blocked both the adenosine- and anoxic-mediated changes in G_w. These data suggest a mechanism involving A₁-receptor-mediated changes in intracellular [Ca²⁺] that result in acute changes in G_w with the onset of anoxia.