146
Xenopus
TABLE 9.1 (Continued)
Ion Current or
Pharmacology
Associated
Characteristics
Associated Diseases
References
Receptor
Gene Found in of the Channel
Oocytes
Organic
Activated by pH
Clcn3
H + /Cl − exchange Dent disease1
( Peshkin et al. 2019 ; Reyes et al. 2004 ;
transporters
changes
Clcn7
transporter,
Cystic f brosis
Ochoa-de la Paz et al. 2013 ) Xenbase
outwardly
Autosomal dominant
Sensitive to La 3+
Tmem184b,
rectifying
Organic solute
Osteopetrosis 2
Amyloidosis Finnish type
( Peshkin et al. 2019 ) Xenbase
Tmem184c
transporter
Mandibulofacial dysostosis
with alopecia
Acrocallosal syndrome
Water
Sensitive to
Aqp1
Water-permeable Blood group Colton system
( Castañeyra-Ruiz et al. 2019 ; Peshkin
(aquaporins)
pCMBS and
Aqp9
channels
Obstructive hydrocephalous
et al. 2019 ; Kalani, et al. 2012 ; Nagahara
phloretin
Hydrarthrosis
et al. 2010 ; Preston et al. 1992 ) Xenbase
polyhydramnios
Glycine receptor Activated by
Glra3
Ionotropic
Susceptibility to epilepsy
( Zeilhofer et al. 2018 ; Peshkin et al. 2019 )
glycine, blocked
receptor
idiopathic generalized 13
Xenbase
by picrotoxin
(Cho et al. 2020). There is also an outwardly rectifying chloride current in X. laevis and X. tropicalis oocytes identif ed
by increasing the concentration of anions in the extracellular
medium (Reyes et al. 2004; Ochoa-de la Paz et al. 2013).
This current corresponds to the chloride/H + exchanger, ClC5, located in the plasma membrane and endosomes, and is
mutated in Dent’s disease, where endocytosis is defective
in renal proximal tubes (Günther et al. 1998; Piwon et al.
2000). Other studies have overexpressed ClC-5 and mutant
versions of the channel overriding the native current, thus
allowing the study of the mutant channel’s characteristics
(Scheel et al. 2005; Chang et al. 2019).
The cacna1c gene encodes for several versions of the voltage-activated calcium channel CaV1.2 subindex. Calcium ions
are important for many cellular functions, including regulating the electrical activity of cells, cell-to-cell communication,
muscle contraction, and gene regulation. In the frog oocyte,
CACNA1C is present and may well provide the entry pathway for calcium necessary for the activation of TMEM16A,
which elicits the transient outward chloride current (T out =
subindex), but this has not been proven (Miledi 1982; Miledi
and Parker 1984). This gene is expressed in heart, muscle, and
brain and is mutated in several conditions such as QT syndrome and Timothy’s syndrome. Other members of the cacna
gene family are expressed in the oocyte, including the P-type
calcium channel (Cacna2d1 and Cacna2d2) related to short
QT syndrome and epilepsy (Antzelevitch et al. 2007; Pippucci
et al. 2013).
Connexins are the main components of gap junctions.
They provide direct links between cells and play a central
role in many cell functions in all tissues; they even participate in transcriptional regulation (Oshima 2014; RibeiroRodrigues et al. 2017; Kim et al. 2019). In the frog oocyte,
Cx43, Cx37, and Cx32 are expressed and modulated by
calcium, magnesium, and negative membrane voltage. Cx43
is involved in oculodentodigital dysplasia and heart malformations, and its activity is exacerbated in many types
of cancer, whereas Cx37 is altered in erythrokeratodermia
(Macari et al. 2000; Kelly et al. 2016).
Aquaporins 1 and 9 have been identifed in Xenopus
oocytes. These water-transporting channels are sensitive to
pCMBSS and phloretin and are associated with obstructive
hydrocephaly (Aquaporin 1) and hydrarthrosis polyhydramnios (Aquaporin 9) (Nagahara et al. 2010; Kalani et al. 2012;
Castañeyra-Ruiz et al. 2019). Aquaporins form a family of
water-permeable channels that were originally cloned from
red blood cells by Peter Agre, who showed that upon overexpression in oocytes, these cells increase the osmotic water
permeability (Preston et al. 1992). Despite the endogenous
expression of aquaporins in frog oocytes, Agre performed
a series of classic experiments to show unequivocally the
functional characteristics of aquaporins.
At least two sodium channels were identifed in the X. tropicalis oocyte proteome: the scnn1b gene, which encodes for
the β subunit of the epithelial sodium channel ENaC, and the
scnn1g gene, which encodes for the γ subunit. ENaC is assembled as a heterotrimer composed of homologous subunits α, β,
and γ or δ, β, and γ. ENaC is constitutively active and is not
voltage dependent like the classic neuronal sodium channels.
Mutations associated with the ENaC genes give rise to Liddle
syndrome, a rare genetic disorder that is characterized by high
blood pressure (hypertension) which is resistant to pharmacological treatment (Yang et al. 2014). The ENaC currents may
well correspond to those previously described (Parker and
Miledi 1987) that are sporadically present in the oocyte and
are resistant to tetrodotoxin. On the other hand, the transient
receptor potential melastatin (TRPM) family belongs to the
superfamily of TRP cation channels. The TRPM subfamily
Xenopus
TABLE 9.1 (Continued)
Ion Current or
Pharmacology
Associated
Characteristics
Associated Diseases
References
Receptor
Gene Found in of the Channel
Oocytes
Organic
Activated by pH
Clcn3
H + /Cl − exchange Dent disease1
( Peshkin et al. 2019 ; Reyes et al. 2004 ;
transporters
changes
Clcn7
transporter,
Cystic f brosis
Ochoa-de la Paz et al. 2013 ) Xenbase
outwardly
Autosomal dominant
Sensitive to La 3+
Tmem184b,
rectifying
Organic solute
Osteopetrosis 2
Amyloidosis Finnish type
( Peshkin et al. 2019 ) Xenbase
Tmem184c
transporter
Mandibulofacial dysostosis
with alopecia
Acrocallosal syndrome
Water
Sensitive to
Aqp1
Water-permeable Blood group Colton system
( Castañeyra-Ruiz et al. 2019 ; Peshkin
(aquaporins)
pCMBS and
Aqp9
channels
Obstructive hydrocephalous
et al. 2019 ; Kalani, et al. 2012 ; Nagahara
phloretin
Hydrarthrosis
et al. 2010 ; Preston et al. 1992 ) Xenbase
polyhydramnios
Glycine receptor Activated by
Glra3
Ionotropic
Susceptibility to epilepsy
( Zeilhofer et al. 2018 ; Peshkin et al. 2019 )
glycine, blocked
receptor
idiopathic generalized 13
Xenbase
by picrotoxin
(Cho et al. 2020). There is also an outwardly rectifying chloride current in X. laevis and X. tropicalis oocytes identif ed
by increasing the concentration of anions in the extracellular
medium (Reyes et al. 2004; Ochoa-de la Paz et al. 2013).
This current corresponds to the chloride/H + exchanger, ClC5, located in the plasma membrane and endosomes, and is
mutated in Dent’s disease, where endocytosis is defective
in renal proximal tubes (Günther et al. 1998; Piwon et al.
2000). Other studies have overexpressed ClC-5 and mutant
versions of the channel overriding the native current, thus
allowing the study of the mutant channel’s characteristics
(Scheel et al. 2005; Chang et al. 2019).
The cacna1c gene encodes for several versions of the voltage-activated calcium channel CaV1.2 subindex. Calcium ions
are important for many cellular functions, including regulating the electrical activity of cells, cell-to-cell communication,
muscle contraction, and gene regulation. In the frog oocyte,
CACNA1C is present and may well provide the entry pathway for calcium necessary for the activation of TMEM16A,
which elicits the transient outward chloride current (T out =
subindex), but this has not been proven (Miledi 1982; Miledi
and Parker 1984). This gene is expressed in heart, muscle, and
brain and is mutated in several conditions such as QT syndrome and Timothy’s syndrome. Other members of the cacna
gene family are expressed in the oocyte, including the P-type
calcium channel (Cacna2d1 and Cacna2d2) related to short
QT syndrome and epilepsy (Antzelevitch et al. 2007; Pippucci
et al. 2013).
Connexins are the main components of gap junctions.
They provide direct links between cells and play a central
role in many cell functions in all tissues; they even participate in transcriptional regulation (Oshima 2014; RibeiroRodrigues et al. 2017; Kim et al. 2019). In the frog oocyte,
Cx43, Cx37, and Cx32 are expressed and modulated by
calcium, magnesium, and negative membrane voltage. Cx43
is involved in oculodentodigital dysplasia and heart malformations, and its activity is exacerbated in many types
of cancer, whereas Cx37 is altered in erythrokeratodermia
(Macari et al. 2000; Kelly et al. 2016).
Aquaporins 1 and 9 have been identifed in Xenopus
oocytes. These water-transporting channels are sensitive to
pCMBSS and phloretin and are associated with obstructive
hydrocephaly (Aquaporin 1) and hydrarthrosis polyhydramnios (Aquaporin 9) (Nagahara et al. 2010; Kalani et al. 2012;
Castañeyra-Ruiz et al. 2019). Aquaporins form a family of
water-permeable channels that were originally cloned from
red blood cells by Peter Agre, who showed that upon overexpression in oocytes, these cells increase the osmotic water
permeability (Preston et al. 1992). Despite the endogenous
expression of aquaporins in frog oocytes, Agre performed
a series of classic experiments to show unequivocally the
functional characteristics of aquaporins.
At least two sodium channels were identifed in the X. tropicalis oocyte proteome: the scnn1b gene, which encodes for
the β subunit of the epithelial sodium channel ENaC, and the
scnn1g gene, which encodes for the γ subunit. ENaC is assembled as a heterotrimer composed of homologous subunits α, β,
and γ or δ, β, and γ. ENaC is constitutively active and is not
voltage dependent like the classic neuronal sodium channels.
Mutations associated with the ENaC genes give rise to Liddle
syndrome, a rare genetic disorder that is characterized by high
blood pressure (hypertension) which is resistant to pharmacological treatment (Yang et al. 2014). The ENaC currents may
well correspond to those previously described (Parker and
Miledi 1987) that are sporadically present in the oocyte and
are resistant to tetrodotoxin. On the other hand, the transient
receptor potential melastatin (TRPM) family belongs to the
superfamily of TRP cation channels. The TRPM subfamily