title: Connexin hemichannels contribute to spontaneous electrical activity in the human fetal cortex.
abstract: Before the human cortex is able to process sensory information, young postmitotic neurons must maintain occasional bursts of action-potential firing to attract and keep synaptic contacts, to drive gene expression, and to transition to mature membrane properties. Before birth, human subplate (SP) neurons are spontaneously active, displaying bursts of electrical activity (plateau depolarizations with action potentials). Using whole-cell recordings in acute cortical slices, we investigated the source of this early activity. The spontaneous depolarizations in human SP neurons at midgestation (17-23 gestational weeks) were not completely eliminated by tetrodotoxin--a drug that blocks action potential firing and network activity--or by antagonists of glutamatergic, GABAergic, or glycinergic synaptic transmission. We then turned our focus away from standard chemical synapses to connexin-based gap junctions and hemichannels. PCR and immunohistochemical analysis identified the presence of connexins (Cx26/Cx32/Cx36) in the human fetal cortex. However, the connexin-positive cells were not found in clusters but, rather, were dispersed in the SP zone. Also, gap junction-permeable dyes did not diffuse to neighboring cells, suggesting that SP neurons were not strongly coupled to other cells at this age. Application of the gap junction and hemichannel inhibitors octanol, flufenamic acid, and carbenoxolone significantly blocked spontaneous activity. The putative hemichannel antagonist lanthanum alone was a potent inhibitor of the spontaneous activity. Together, these data suggest that connexin hemichannels contribute to spontaneous depolarizations in the human fetal cortex during the second trimester of gestation.
authors.affiliation: Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06030.
authors.forename: Anna R
authors.initials: AR
authors.lastname: Moore
authors.affiliation: Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06030.
authors.forename: Wen-Liang
authors.initials: WL
authors.lastname: Zhou
authors.affiliation: Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06030.
authors.forename: Carissa L
authors.initials: CL
authors.lastname: Sirois
authors.affiliation: Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06030.
authors.forename: Glenn S
authors.initials: GS
authors.lastname: Belinsky
authors.affiliation: Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06030.
authors.forename: Nada
authors.initials: N
authors.lastname: Zecevic
authors.affiliation: Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06030 antic@neuron.uchc.edu.
authors.forename: Srdjan D
authors.initials: SD
authors.lastname: Antic
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000196:embryology* / Q000502:physiology*; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D055724:Electrophysiological Phenomena / Q000187:drug effects; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000502:physiology*; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology; D005865:Gestational Age; D006801:Humans; D007811:Lanthanum / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26; D007811:Lanthanum; D002118:Calcium
keywords: GABA; UP states; brain development; glutamate; preterm infants