Excitable properties in astrocytes derived from human embryonic CNS stem cells

Although it is widely believed that astrocytes lack excitability in adult t issue, primitive action potential-like responses have been elicited from ho lding potentials negative to -80 mV, in cultured and injury-induced gliotic rodent astrocytes and in human glia under pathological conditions such as glioblastomas and temporal lobe epilepsy. The present study was designed to investigate the properties of astrocytes (identified by immunoreactivity f or glial fibrillary acidic protein) derived from multipotent human embryoni c CNS stem cells and cultured for 12-25 days in differentiating conditions. We describe here for the first time that brief (1 ms) current pulses elici t spikes from a resting potential (V-REST) of approximate to -37 mV and, mo re interestingly, that spontaneous firing can be occasionally recorded in h uman astrocytes. A voltage-clamp study revealed that in these cells: (i) th e half-inactivation of the tetrodotoxin (TTX)-sensitive Na+ channels is aro und V-REST; (ii) the delayed rectifier K+ current is very small; (iii) the ever-present transient outward A-type K+ channels are paradoxically capable of inhibiting the action potentials elicited from a negative membrane pote ntial (-55 to -60 mV); and (iv) inwardly rectifying currents are not presen t. The responses predicted from a simulation model are in agreement with th e experiments. As suggested by recent studies, the decrease of Na+ channel expression and the changes of the electrophysiological properties during th e postnatal maturation of the CNS seem to exclude the possibility that astr ocytes may play an excitable role in adult tissue. Our data show that excit ability and firing should be considered an intrinsic attribute of human ast rocytes during CNS development. This is likely to have physiological import ance because the role of astrocytes during development is different from th e [K+](o)-buffering role played in adult CNS, namely the glutamate release and/or the guiding of migrating neurons.