Abstract
Intracellular recordings were made from CA1 pyramidal neurons in rat hippocampal tissue slices. Administration of oxygen- and glucose-deprived medium (in vitro ischemia) produced a rapid depolarization after 5 – 6 min exposure. When oxygen and glucose were reintroduced immediately after the rapid depolarization, the membrane depolarized further and reached 0 mV (irreversible membrane dysfunction) 5 min after the reintroduction. In the present study, we examined the contribution of protein kinase A (PKA) activation to the irreversible membrane dysfunction. In the majority of CA1 neurons pretreated with PKA inhibitor (H89; 1 μM) the membrane was restored to the preexposure potential level after the reintroduction. Pretreatment with adenylyl cyclase inhibitor (SQ22536; 100 μM or Rp-cAMPS; 100 μM) also restored the membrane to the preexposure level. Pretreatment with calmodulin inhibitor (W-7; 50 μM), but not calmodulin kinase II inhibitor (KN62; 10 μM) or myosin light chain kinase inhibitor (ML-7; 10 μM), restored the membrane to the preexposure level. These results suggest that the activation of PKA via calcium calmodulin complex (Ca2+/CaM) produces the irreversible membrane dysfunction following in vitro ischemia. [Jpn J Physiol 54 Suppl:S157 (2004)]
