. 2014 Nov 4;8:348. doi: 10.3389/fncel.2014.00348

Table 2.

Roles of connexin hemichannels and pannexin channels in neurophysiology.

Function	Channel subtype	Proposed mechanisms	Experimental models and tools	References
DEVELOPMENT AND GLUCOSE SENSING
(1) Development
↑ Cell division and proliferation	Cx43	ATP released from RPE cells via Cx43 HCs triggers Ca²⁺ waves through RPE cells and stimulates P2 receptors on retinal progenitor cells	Isolated neural retina from chick embryos	Pearson et al., 2005
	Cx43		Pharmacological blocker (Carbenoxolone); mimetic peptide (Gap26)	Pearson et al., 2005
	Panx1	ATP released via Panx1 channels stimulates NSC/NPC via P2 receptors	Neuro2a neuroblastoma cell line, cultures of postnatal mouse ventricular zone NSC/NPCs	Wicki-Stordeur et al., 2012
	Panx1		Pharmacological blocker (Probenecid); Panx1 siRNA	Wicki-Stordeur et al., 2012
(2) Glucose sensing and signal transduction
↑ Hypothalamic glucose-sensing	Cx43	Glucose uptake and glycolysis opens Cx43 HCs allowing the release of ATP, which activates local P2Y1 receptors and [Ca²⁺]_i increase	Cultured rat hypothalamic tanycytes	Orellana et al., 2012a
↑ Hypothalamic glucose-sensing	Cx43		Pharmacological blockers (La³⁺, Cx43^E2, Probenecid); mimetic peptides (Gap26, ¹⁰panx)	Orellana et al., 2012a
↑ Metabolic autocrine regulation	Panx1	Decrease in extracellular glucose triggers the opening of Panx1 channels through which ATP is released	Acute hippocampal slices from juvenile rats	Kawamura et al., 2010
↑ Metabolic autocrine regulation	Panx1		Pharmacological blocker (Carbenoxolone, Octanol); mimetic peptide (¹⁰panx)	Kawamura et al., 2010
SYNAPTIC TRANSMISSION AND PLASTICITY
(1) Neuronal excitability and synaptic transmission
↑ Synaptic transmission	Cx43	ATP released via Cx43 HCs in astrocytes promotes excitatory synaptic transmission via P2 receptors	Acute hippocampal slices from juvenile mice	Chever et al., 2014
↑ Synaptic transmission	Cx43		Transgenic mice: Cx43^fl/fl:hGFAP-Cre = Astrocytic Cx43 conditional knockout; pharmacological blocker (Carbenoxolone), mimetic peptide (Gap26, ¹⁰panx)	Chever et al., 2014
↑ Feedback inhibitory synaptic transmission	Cx43	Decrease in [Ca²⁺]_e during excitatory transmission opens Cx43 HCs in astrocytes allowing the release of ATP, which triggers depolarization and firing of inhibitory interneurons and a slow Ca²⁺ wave in astrocytes both via P2Y receptors	Acute hippocampal slices from juvenile mice	Torres et al., 2012
↑ Feedback inhibitory synaptic transmission	Cx43		Transgenic mice: (1) Cx30^−/−Cx43^fl/fl:hGFAP-Cre = Cx30 total- and Cx43 astrocytic conditional knockout; (2) Cx30^−/−Cx43^fl/fl = Cx30 total knockout; and 3) Cx43⁺/G138Rfl:hGFAP-Cre mice = enhanced astrocytic Cx43 HC activity; pharmacological blocker (Carbenoxolone)	Torres et al., 2012
↓ Neuronal excitability	Panx1	Decrease in extracellular glucose triggers the opening of Panx1 channels through which ATP is released. Its metabolite adenosine then activates adenosine A1 receptors and opens K_ATP channels leading to decreased neuronal excitability	Acute hippocampal slices from juvenile rats	Kawamura et al., 2010
↓ Neuronal excitability	Panx1		Pharmacological blocker (Carbenoxolone, Octanol); mimetic peptide (¹⁰panx)	Kawamura et al., 2010
↓ Synaptic transmission	Panx1	Adenosine metabolized from ATP released via Panx1 channels decreases neurotransmission	Acute hippocampal slices from adult mice	Prochnow et al., 2012
	Panx1		Transgenic mice: Panx1^−/− (Panx1 knockout)	Prochnow et al., 2012
	Panx1	Panx1 channels decrease neurotransmission in adult but not young mice	Acute hippocampal slices from young and adult mice	Ardiles et al., 2014
	Panx1		Transgenic mice: Panx1^−/− (Panx1 knockout); Pharmacological blocker (Probenecid)	Ardiles et al., 2014
↑ Light-induced feedback transmission	Cx55.5	Cx55.5 HC current at the tips of the horizontal cell dendrites induces local voltage drop near voltage dependent Ca²⁺ channels of cones mediating feedback ephaptic transmission	Isolated retina, dissociated horizontal cells and cones from zebrafish	Klaassen et al., 2011
↑ Light-induced feedback transmission	Cx55.5		Transgenic zebrafish: Cx55.5 mutant (no functional Cx55.5 protein formation)	Klaassen et al., 2011
↓ Spontaneous neuronal activity	Panx1	Panx1 channels on active neurons promote microglial motility via ATP/P2 receptors, which in turn downregulates spontaneous neuronal activity	Zebrafish larvae	Li et al., 2012
↓ Spontaneous neuronal activity	Panx1		Pharmacological blocker (Carbenoxolone, Probenecid); Panx1 downregulation oligonucleotides	Li et al., 2012
(2) Synaptic plasticity
↓ LTP	Panx1	Adenosine metabolized from ATP released via Panx1 channels suppresses the induction of LTP	Acute hippocampal slices from adult mice	Prochnow et al., 2012
↓ LTP	Panx1		Transgenic mice: Panx1^−/− (Panx1 knockout); Pharmacological blocker (mefloquine)	Prochnow et al., 2012
↓ LTP, ↑ LTD	Panx1	Panx1 channels control the threshold of the bidirectional induction of synaptic plasticity in adult but not in young mice	Acute hippocampal slices from young and adult mice	Ardiles et al., 2014
↓ LTP, ↑ LTD	Panx1		Transgenic mice: Panx1^−/− (Panx1 knockout); Pharmacological blocker (Probenecid)	Ardiles et al., 2014
INTEGRATIVE FUNCTIONS
(1) Sensorimotor gating
↓ Sensorimotor gating capabilities	Panx1	Panx1 channels inhibit pre-pulse inhibition of the acoustic startle response	Mice (adult)	Prochnow et al., 2012
↓ Sensorimotor gating capabilities	Panx1		Transgenic mice: Panx1^−/− (Panx1 knockout)	Prochnow et al., 2012
(2) Learning and memory
↑ Fear memory consolidation	Cx43	Gliotransmitters release through astrocytic Cx43 HCs promotes the consolidation of fear memory	Rats (adult)	Stehberg et al., 2012
↑ Fear memory consolidation	Cx43		Mimetic peptides injection into basolateral amygdala (Gap26, TAT-Cx43L2)	Stehberg et al., 2012
↑ Object recognition memory	Panx1	Panx1 channels improve the ability of a mouse to recognize an object as familiar	Mice (adult)	Prochnow et al., 2012
↑ Object recognition memory	Panx1		Transgenic mice: Panx1^−/− (Panx1 knockout)	Prochnow et al., 2012
↑ Spatial memory	Panx1	Panx1 channels enhance the ability of a mouse to remember the location of a treat	Mice (adult)	Prochnow et al., 2012
↑ Spatial memory	Panx1		Transgenic mice: Panx1^−/− (Panx1 knockout)	Prochnow et al., 2012
(3) Vision
↑ Contrast sensitivity	Cx55.5	Cx55.5 HC mediated feedback from horizontal cells to cones leads to contrast enhancement	Zebrafish larvae	Klaassen et al., 2011
↑ Contrast sensitivity	Cx55.5		Transgenic zebrafish: Cx55.5 mutant zebrafish (no functional Cx55.5 protein formation)	Klaassen et al., 2011
↓ Visually-evoked neuronal activity	Panx1	Microglial contact promoted by Panx1 channels on active neurons via ATP/P2 receptors downregulates evoked neuronal activity	Zebrafish larvae	Li et al., 2012
↓ Visually-evoked neuronal activity	Panx1		Pharmacological blocker (Carbenoxolone, Probenecid); Panx1 downregulation oligonucleotides	Li et al., 2012

Cx, Connexin; fl, floxed; HC, hemichannel; G138R, single point mutation of glycine 138 to arginine of Cx43; LTD, long-term depression; LTP, long-term potentiation; NSC/NPS, neural stem cells and progenitor cells; Panx, Pannexin; RPE, retinal pigment epithelium.