Sodium and Potassium e Channels and Pumps - Biological Inorganic Chemistry - page 184

We saw earlier how the 3-D structure of a two transmembrane bacterial K þ channel, KcsA, analogous to the
inwardly rectifying K þ channels, reveals an 'inverted tepee' arrangement around a central pore, with the narrow
outer mouth of the pore formed by the pore loop ( Figure 9.7 ) . Information on how the pore might be opened comes

FIGURE 9.7 Structures of potassium channels in open and closed conformations. The selectivity filter is orange, and the conserved glycine
residue, which is thought to be critical for the bending of the M2 helix in the open conformation, is in red. (From Yu, Yarov-Yarovoy, Gutman, &

Catterall, 2005 . Reproduced with permission of Blackwell Publishing Ltd.)

from the structure of a bacterial 2TM calcium-activated K þ channel, MthK ( Figure 9.7 ), analysed in its calcium-
bound, presumably open, form. The M2 helices are bent at a highly conserved glycine residue, and this bend
appears to open the intracellular mouth of the pore sufficiently to allow permeation of ions.

SODIUM CHANNELS
The sodium channels ( Catterall, 2000 ) consist of a highly processed

a subunit (260 kDa), associated with auxiliary

b -subunit is sufficient for functional expression, but the kinetics and voltage

dependence of channel gating are modified by the

subunits. The pore-forming a

b subunits. The transmembrane organisation is shown in

Figure 9.8 . The a -subunit is organised in four homologous domains (I e IV), each consisting of six transmembrane

a S6) and an additional pore loop located between the S5 and S6 helices, each similar to the indi-

vidual subunits of the 6TM K þ channels. The pore loops line the outer, narrow entry to the pore, while the S5 and
S6 helices line the inner, wider exit from the pore. The S4 segments in each domain contain positively charged
amino acids in every third position. These residues serve as gating charges and move across the membrane to
initiate channel activation in response to depolarisation of the membrane. A short intracellular loop connecting the
domains III and IV serves as the inactivation gate, folding into the channel structure and blocking the pore from
the inside during sustained depolarisation of the membrane. It contains an Ile

helices (S1 e

Thr (IFMT) motif,
which is crucial for inactivation. The circles in the re-entrent loops in each of the four domains represent the amino
acids that form the ion selectivity filter: the outer rings have the sequence EEDD and the inner rings DEKA.

e Phe e Met e

THE SODIUMePOTASSIUM ATPASE
Mammalian cells maintain a lower concentration of Na þ (around 12 mM) and a higher concentration of K þ
(around 140 mM) than in the surrounding extracellular medium (respectively 145 mM and 4 mM). The Na þ -K þ -
ATPase which maintains high intracellular K þ and low intracellular Na þ is localised in the plasma membrane, and
belongs to the family of P-type ATPases. Other members of the family in eukaryotes are the sarcoplasmic