您的位置： 百康网 > 期刊 > 药学 > 《药理学进展》 > 2005年12月第4期 > 正文
International Union of Pharmacology. LII. Nomenclature and Molecular Relationships of Calcium-Activated Potassium Channels
http://www.100kang.com 2007-6-8 10:53:50 LII


Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri (A.D.W.); Departments of Microbiology and Molecular Genetics (G.A.G.) and Physiology and Biophysics (K.G.C.), University of California, Irvine, Irvine, California; Molecular and Cellular Physiology Department, Stanford University, Stanford, California (R.A.); Department of Medical Pharmacology and Toxicology, University of California, Davis, Davis, California (H.W.); and Department of Applied Physiology, University Ulm, Ulm, Germany (S.G.)

Introduction

Introduction

The second major group of six/seven transmembrane potassium-selective channels consists of the KCa channels (for reviews, see Lingle, 2002; Magleby, 2003; Moczydlowski, 2004; Stocker, 2004; Cox, 2005), and Table 1 shows the International Union of Pharmacology (IUPHAR1) names of the members of this group together with their HUGO Gene Nomenclature Committee (HGNC) designations and other commonly used names. The phylogenetic trees in Fig. 1 illustrate the fact that these channels form two well defined but only distantly related groups.

TABLE 1 KCa channels IUPHAR names of the members of the KCa group of potassium channels are shown, together with their HGNC designations and other commonly used names.

FIG. 1. Phylogenetic tree for KCa channels. A, KCa2/3 group. B, KCa1/4/5 group. Amino acid sequence alignments and phylogenetic analysis for these two groups of four human KCa channels were generated as described in the legend for Fig. 1 of "International of Union of Pharmacology LIII. Nomenclature and Molecular Relationships of Voltage-Gated Potassium Channels." No new channels have been added to these topologies since they appeared in the earlier edition of this compendium. IUPHAR and HGNC names of the genes are shown together with other commonly used names and their chromosomal localization.

One of these groups (Fig. 1A) includes the three "small-conductance" KCa channels (KCa2.1, 2.2, and 2.3) (Kohler et al., 1996) and the "intermediate-conductance" channel KCa3.1 (Ishii et al., 1997; Joiner et al., 1997). These channels are voltage-insensitive and are activated by low concentrations of internal Ca2+ (<1.0 μM), in contrast to KCa1.1 (KCNMA1, Slo1), which is activated by both voltage and internal Ca2+. The three small-conductance KCa channels are sensitive to block by apamin (100 pM–10 nM), which distinguishes them from all other KCa channels. Both small- and intermediate-conductance KCa channels play important roles in many processes involving Ca2+-dependent signaling in both electrically excitable and nonexcitable cells. They do not bind Ca2+ directly but rather detect Ca2+ by virtue of calmodulin, which is constitutively bound to the C-terminal region (Xia et al., 1998; Fanger et al., 1999). Binding of calcium to this calmodulin results in conformational changes that are in turn responsible for channel gating (Schumacher et al., 2001).

The tree shown in Fig. 1B illustrates the sequence relationships within the second group of KCa channels, which includes KCa1.1 (Slo or Slo1), KCa4.1 (Slack or Slo2.2), KCa4.2 (Slick or Slo2.1), and KCa5.1 (Slo3). KCa1.1 has been extensively studied in the brain, cochlea, and muscle, and alternate splicing of its mRNA is known to produce considerable functional diversity (Weiger et al., 2002; Faber and Sah, 2003). Unlike the KCa2 and KCa3 channels, binding of calcium by KCa1.1 is not dependent on its association with calmodulin but is thought to be mediated by at least three divalent cation binding sites in the cytoplasmic carboxyl domain of each channel subunit. Two independent high-affinity Ca2+ binding sites are formed by a negatively charged segment in the distal carboxyl terminal portion, termed the "calcium bowl" (Schreiber and Salkoff, 1997) and within the first RCK domain encoded by the proximal C-terminal portion (Bao et al., 2002; Xia et al., 2002). A third low-affinity divalent cation binding site is also found in the first RCK domain (Shi et al., 2002), which contributes to activation by Mg2+ and Ca2+ at high concentrations (>1 mM).

The three other members of this group, KCa4.1, 4.2, and 5.2 (Joiner et al., 1997; Schreiber et al., 1998; Yuan et al., 2003), were all included in the KCa nomenclature since they all are clearly members of this structurally related group of genes. However, much more is now known about the functional properties of the members of this gene family than was known when these names were assigned several years ago, and this presents a possible conundrum for a nomenclature based on functional rather than structural similarity. Unlike the founding member KCa1.1, which is in fact activated by internal Ca2+, none of the other members of this group seems to be similarly Ca2+-activated. In fact, for the most part, these three are insensitive to internal Ca2+. KCa4.2 and KCa4.1 are activated by internal Na+ and Cl- (Yuan et al., 2003), and KCa5.1 is activated by internal alkalization (OH-) (Schreiber et al., 1998). Therefore, although they are structurally related to KCa1.1, these three channels cannot correctly be described as "calcium-activated" channels based on functional criteria. This may be a subject for discussion among researchers in this field and those bodies responsible for standardizing gene nomenclature.

Tables 2, 3, 4, 5, 6, 7, 8, 9 present the KCa1.1 through KCa 5.1 channels.

TABLE 2 KCa1.1 channels

TABLE 3 KCa2.1 channels

TABLE 4 KCa2.2 channels

TABLE 5 KCa2.3 channels

TABLE 6 KCa3.1 channels

TABLE 7 KCa4.1 channels

TABLE 8 KCa4.2 channels

TABLE 9 KCa5.1 channels

Address correspondence to: Dr. Aguan D. Wei, Department of Anatomy and Neurobiology, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110. E-mail: a.wei@wustl.edu

References

Bao L, Rapin AM, Holmstrand EC, and Cox DH (2002) Elimination of the BKCa channel's high-affinity Ca2+ sensitivity. J Gen Physiol 120: 173-189.

Cox DH (2005) The BKCa channel's Ca2+-binding sites, multiple sites, multiple ions. J Gen Physiol 125: 253-255.

Faber ESL and Sah P (2003) Calcium-activated potassium channels: multiple contributions to neuronal function. Neuroscientist 9: 181-194.

Fanger CM, Ghanshani S, Logsdon NJ, Rauer H, Kalman K, Zhou J, Beckingham K, Chandy KG, Cahalan MD, and Aiyar J (1999) Calmodulin mediates calcium-dependent activation of the intermediate conductance KCa channel, IKCa1. J Biol Chem 274: 5746-5754.

Ishii TM, Silvia C, Hirschberg B, Bond CT, Adelman JP, and Maylie J (1997) A human intermediate conductance calcium-activated potassium channel. Proc Natl Acad Sci USA 94: 11651-11656.

Joiner WJ, Tang MD, Wang LY, Dworetzky SI, Boissard CG, Gan L, Gribkoff VK, and Kaczmarek LK (1998) Formation of intermediate-conductance calcium-activated potassium channels by interaction of Slack and Slo subunits. Nat Neurosci 1: 462-469.

Joiner WJ, Wang LY, Tang MD, and Kaczmarek LK (1997) hSK4, a member of a novel subfamily of calcium-activated potassium channels. Proc Natl Acad Sci USA 94: 11013-11018.

Kohler M, Hirschberg B, Bond CT, Kinzie JM, Marrion NV, Maylie J, and Adelman JP (1996) Small-conductance, calcium-activated potassium channels from mammalian brain. Science 273: 1709-1714.

Lingle CJ (2002) Setting the stage for molecular dissection of the regulatory components of BK channels. J Gen Physiol 120: 261-265.

Magleby KL (2003) Gating mechanism of BK (Slo1) channels: so near, yet so far. J Gen Physiol 121: 81-96.

Moczydlowski EG (2004) BK channel news: full coverage on the calcium bowl. J Gen Physiol 123: 471-473.

Schreiber M and Salkoff L (1997) A novel calcium-sensing domain in the BK channel. Biophys J 73: 1355-1363.

Schreiber M, Wei A, Yuan A, Gaut J, Saito M, and Salkoff L (1998) Slo3, a novel pH-sensitive K+ channel from mammalian spermatocytes. J Biol Chem 273: 3509-3516.

Schumacher MA, Rivard AF, Bachinger HP, and Adelman JP (2001) Structure of the gating domain of a Ca2+-activated K+ channel complexed with Ca2+/calmodulin. Nature (Lond) 410: 1120-1124.

Shi J, Krishnamoorthy G, Yang Y, Hu L, Chaturvedi N, Harilal D, Qin J, and Cui J (2002) Mechanism of magnesium activation of calcium-activated potassium channels. Nature (Lond) 418: 876-880.

Stocker M (2004) Ca2+-activated K+ channels: molecular determinants and function of the SK family. Nat Rev Neurosci 5: 758-770.

Weiger TM, Hermann A, and Levitan IB (2002) Modulation of calcium-activated potassium channels. J Comp Physiol A Neuroethol Sens Neural Behav Physiol 188: 79-87.

Xia XM, Fakler B, Rivard A, Wayman G, Johnson-Pais T, Keen JE, Ishii T, Hirschberg B, Bond CT, Lutsenko S, et al. (1998) Mechanism of calcium gating in small-conductance calcium-activated potassium channels. Nature (Lond) 395: 503-507.

Xia XM, Zeng X, and Lingle CJ (2002) Multiple regulatory sites in large-conductance calcium-activated potassium channels. Nature (Lond) 418: 880-884.

Yuan A, Santi CM, Wei A, Wang ZW, Pollak K, Nonet M, Kaczmarek L, Crowder CM, and Salkoff L (2003) The sodium-activated potassium channel is encoded by a member of the Slo gene family. Neuron 37: 765-773.


  
《药理学进展》医学期刊2005年12月第57卷第4期