Intercellular communication in spinal cord astrocytes: Fine tuning betweengap junctions and P2 nucleotide receptors in calcium wave propagation

Electrophysiological properties of gap junction channels and mechanisms inv olved in the propagation of intercellular calcium waves were studied in cul tured spinal cord astrocytes from sibling wild-type (WT) and connexin43 (Cx 43) knock-out (KO) mice. Comparison of the strength of coupling between pai rs of WT and Cx43 KO spinal cord astrocytes indicates that two-thirds of to tal coupling is attributable to channels formed by Cx43, with other connexi ns contributing the remaining one-third of junctional conductance. Although such a difference in junctional conductance was expected to result in the reduced diffusion of signaling molecules through the Cx43 KO spinal cord sy ncytium, intercellular calcium waves were found to propagate with the same velocity and amplitude and to the same number of cells as between WT astroc ytes. Measurements of calcium wave propagation in the presence of purinocep tor blockers indicate that calcium waves in Cx43 KO spinal cord astrocytes are mediated primarily by extracellular diffusion of ATP; measurements of r esponses to purinoceptor agonists revealed that the functional P2Y receptor subtype is shifted in the Cx43 KO astrocytes, with a markedly potentiated response to ATP and UTP. Thus, the reduction in gap junctional communicatio n in Cx43 KO astrocytes leads to an increase in autocrine communication, wh ich is a consequence of a functional switch in the P2Y nucleotide receptor subtype. Intercellular communication via calcium waves therefore is sustain ed in Cx43 null mice by a finely tuned interaction between gap junction-dep endent and independent mechanisms.