Figure 1.

The effect of blockers of pannexin hemichannels and of glutamate and GABA receptors on the anoxic depolarization current with 4 mM ATP in the pipette solution (slices from P12 rats). (A) Response of a CA1 pyramidal cell at −33mV to simulated ischaemia. After 5–7 min of ischaemia, a large inward current develops. (B) As A, but with the pannexin hemichannel blocker carbenoxolone (100 µM) in the external and pipette solutions. (C) As A, but with the pannexin hemichannel blocker La³⁺ (100 µM) in the external solution. (D) As A, but with the pannexin hemichannel blocker mefloquine (25 µM) in the external solution. (E) As A, but with NMDA, AMPA, kainate and GABA_A receptor blockers [50 µM D-AP5, 50 µM MK-801, 25 µM 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo[f]quinoxaline-2,3-dione (NBQX), 100 µM 7-chlorokynurenate (7-CK) and 100 µM bicuculline (BIC)] present from the onset of ischaemia. (F) As E, but with application of carbenoxolone (Cbx) + La³⁺ and of mefloquine (Mfq), to test whether the small inward current occurring in the presence of the transmitter receptor blockers reflects pannexin activation (note different time scale). (G and H) Quantification of the effect of hemichannel and receptor blockers on the current evoked by ischaemia, for experiments as in panels A–E. (G) Maximum inward current, relative to the current level before ischaemia [i.e. the peak of the anoxic depolarization (AD) current, except in the presence of glutamate/GABA_A receptor blockers when, because no anoxic depolarization occurred, the maximum inward current reached within 15 min after the start of ischaemia was measured]. (H) Inward current (relative to the current level before ischaemia) measured 5 min after the anoxic depolarization (not shown for the presence of glutamate/GABA_A receptor blockers as no anoxic depolarization occurred). Number of cells studied is indicated above each bar. P-values are for comparison without blockers. con = control; GluR = glutamate receptor; GABA_AR = GABA_A receptor.