Table 3

Subclasses within structural class 1

1.1 Superfamily of Cys-loop receptors
(Cockcroft et al., 1990;Karlin and Akabas, 1995) Includes ion channels gated by GABA, glycine, 5-HT, acetylcholine (nicotinic), and glutamate (anion channel) (Nistri and Arenson, 1983; Cully et al., 1994,1996)1.1 1.1 1.1 1.1 1.1 GABA GLY GLU ACH 5HT
1.2 Glutamate-gated cation channels
Includes NMDA and non-NMDA receptors1.2GLU
1.3 Related to voltage-gated cation channels
Includes receptors for cyclic nucleotides and for IP3 as well as the “ryanodine receptor”3-a 1.3IP3
1.4 Related to epithelial Na+ channels; non-peptide–gated
Includes P2X receptors for ATP (North and Barnard, 1997) and proton-gated cation channels (Waldmann et al., 1997)1.4NUCT
1.5 Related to epithelial Na+channels; peptide-gated
e.g., FMRF-gated Na+channel (Lingueglia et al., 1995)1.5FMRF
1.63-b Related to inward rectifier K+channels
e.g., ATP-activated K+ channel (Lesageet al., 1995; Takumi et al., 1995) and the ATP-antagonized K+ channel (K ATP) (Clement et al., 1997; Gribble et al., 1997;Tucker et al., 1997)3-c 1.6NUCT
1.73-b Related to ATPase-linked transporters
e.g., CFTR (ATP-activated anion channel) (Baukrowvitz et al., 1994)3-d 1.7NUCT
1.83-b Related to neurotransmitter transporters
e.g., glutamate-activated chloride channel/EAA transporter (Fairman et al., 1995; Picaud et al., 1995)3-d 1.8GLU

(ion-channel receptors)

  • 3-a It should be noted that subclass 1.3 will contain at least two protein superfamilies, which do not share any sequence homology. One comprises the cyclic nucleotide receptors and the second comprises the IP3 and the ryanodine receptors.

  • 3-b It is recognized that the definition of subclasses 1.6, 1.7, and 1.8 may require modification as knowledge of them increases, but they serve to illustrate the full potential of the proposed coding system.

  • 3-c Several KATP channel subtypes are known in different tissues, differing greatly in their response to inhibitory sulfonyl ureas (SUR) and to channel-opening drugs such as diazoxide. Their structures, as known so far by DNA cloning, contain two unrelated subunits, an inward rectifier K+ channel protein (from the Kir.6 series) and a sulfonylurea- and nucleotide-binding protein (SUR); a family of SURs produce variations in the KATPpharmacology (Inagaki et al., 1996). Therefore,KATP channel subunits will be numbered in two series; for the KIR (6.1), etc., subunits as 1.6.KIR.61.S [or 62.S, etc.] and for the SUR1, etc., subunits 1.6.SUR.01.S [or 02.S etc.], and the entire KATP channel as 1.6.NUCT.01.M [or 02.M, etc.] when definitive evidence for the subunit composition is known.

  • 3-d Although genes for types 1.7 and 1.8 have each been cloned, expressed, and shown to correspond to channels seen in native tissues (Baukrowvitz et al., 1994; Fairman et al., 1995), the precise relationship of the ion channel to the transporter in these types is at present unclear. Transporters are not necessarily ligand-gated channels: however, in addition to the case of glutamate transporters, transporters of serotonin (5-HT) and of dopamine incorporate, respectively, a 5-HT-gated channel (Galli et al., 1997) or a dopamine-gated channel (Sonders et al., 1997), and this principle may hold also for norepinephrine and γ-aminobutyric acid transporters (Sonders and Amara, 1996).