Molecular and functional diversity of neural connexins in the retina

Electrical synapses (gap junctions) in neuronal circuits have become a majo r focus in the study of network properties such as synchronization and osci llation (Galarreta and Hestrin, 1999; Gibson et al., 1999). Despite the rec ent progress made in unraveling the contribution of gap junctions to networ k behavior, little is known about the molecular composition of the junction al constituents. By cloning gap junction proteins [connexins (Cxs)] from ze brafish retina and through functional expression, we demonstrate that the r etina possesses a high degree of connexin diversity, which may account for differential functional properties of electrical synapses. Three new Cxs, d esignated as zebrafish Cx27.5 (zfCx27.5), zfCx44.1, and zfCx55.5, and the c arp ortholog of mammalian Cx43 were cloned. By in situ hybridization and in situ RT-PCR, we demonstrate that the four fish connexin mRNAs show differe ntial localization in the retina. Transient functional expression in paired Xenopus oocytes and in the neuroblastoma N2A cell line indicate an extreme range of electrophysiological properties of these connexins in terms of vo ltage dependence and unitary conductance. For instance, the new zfCx44.1 ex hibited high sensitivity to voltage-induced closure with currents decaying rapidly for transjunctional potentials >10 mV, whereas zfCx55.5 channels sh owed an opposite voltage dependence in response to voltage steps of either polarity. Moreover, although zfCx44.1 channels showed unitary conductance a s high as any previously reported for junctional channels (nearly 300 pS), zfCx55.5 and zfCx27.5 exhibited much lower unitary conductances (<60 pS).