CALCIUM WAVES BETWEEN ASTROCYTES FROM CX43 KNOCKOUT MICE

Gap junctions are regarded as the primary pathway underlying propagati on of Ca2+ waves between astrocytes, although signaling through extrac ellular space may also contribute. Results obtained from astrocytes cu ltured from sibling Cx43 knockout (KO) and wild-type (WT) mice in six litters showed that Ca2+ waves propagated more slowly in Cx43 KO than in WT astrocytes; however, because this difference in velocity was onl y seen in conditions where cell confluence was higher in WT than KO as trocytes, it is attributable to differences in plating density. By con trast, density-independent differences were observed in the amplitudes of the Ca2+ responses (15% smaller in KO astrocytes) and efficacy of spread (to 14% fewer cells in KO astrocytes). Blockade of purinergic r eceptors with suramin reduced the velocities of the waves by 40% in WT and KO astrocytes and reduced the amplitudes by 20% and 6%, respectiv ely. In the presence of heptanol, Ca2+ waves spread to only 30% of the cells, with a 70% reduced velocity and 30% reduced amplitude. It is c oncluded that the propagation of Ca2+ waves between astrocytes from Cx 43 KO mice is not so greatly affected as expected by deletion of the m ajor gap junction protein between these cells. The residual 5% couplin g contributed by the additional connexins (Cx40, Cx45, and Cx46) expre ssed in KO astrocytes still suffices to provide a more substantial por tion of Ca2+ wave propagation than does signaling through extracellula r purinergic pathways. These studies demonstrate that, even with sever ely reduced junctional conductance, Cx43 KO astrocytes are capable of performing long-range Ca2+ wave signaling, perhaps preserving one mech anism critical to neural function. GLIA 24:65-73, 1998. (C) 1998 Wiley -Liss, Inc.