Page 73 - Academic Press Encyclopedia of Physical Science and Technology 3rd BioChemistry

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Encyclopedia of Physical Science and Technology EN008K-353 June 29, 2001 12:41

106 Ion Transport Across Biological Membranes

How is the signal that was initiated by neurotransmitter-
mediated reactions propagated? In general, cell mem-
branes are more permeable to potassium ions, which are at
a higher concentration inside the cell membrane than out-
side and bound to immobile cations, mainly amino acids
and proteins. The outflow of potassium ions along their
concentration gradient is counteracted by the transmem-
brane voltage that is created by this outflow. The equi-
librium potential for potassium ions, for instance, E K ,is
+
given by the Nernst equation (Eq. 1). The resting trans-
membrane potential of neurons is around −60 mV.
When the flux of ions through neurotransmitter recep-
tor channels results in a change (of ∼20 mV) in the trans-
FIGURE 7 The selectivity filter of the potassium channel
membrane voltage to a more positive V m value, the electri- based on the X-ray crystallographic structure determination by
cal signal is propagated along the axon of the cell within MacKinnon and colleagues. The potassium channel is tetrameric
1 msec. This occurs in the following way. At a critical with a hole in the middle that forms the ion pore. Each subunit
value of V m , specific voltage-dependent Na transmem- forms two transmembrane helices, the inner and the outer helix.
+
The pore helix and loop regions build up the ion pore in combi-
brane channels in the axonal membrane open, allowing
nation with the inner helix. The black spheres in the middle of the
sodium ions to flow inside the axon (Fig. 1). As the inward channel represent potassium ions. (Reproduced with permission
flow of sodium ions changes V m to even more positive from Branden, C., and Tooze, J. (1999). Fig. 12.11, p. 233. In “In-
+
values, the Na -specific channels are inactivated. Trans- troduction to Protein Structure,” 2nd edition, Garland Publishing,
membrane K channels open, changing V m again to more New York.)
+
negative values. This in turn leads again to the opening of
voltage-dependent Na -specific channels. These changes
+
in transmembrane voltage, called action potentials, are quences and properties are also present in other organ-
propagated along the axon to the nerve terminal adja- isms. The bacterial K channel contains 158 amino acid
+
cent to another cell. Axons range from 0.1 mm to over residues. Four subunits are arranged around a central axis
1 m in length and can convey electrical signals within to form the channel. The K channel has two transmem-
+
1 msec. When the signal arrives at the nerve terminal, brane helices.
Ca -specific transmembrane channels open and the in- Thestructuregivesanimportantindicationastohowthe
2+
˚
flux of calcium ions leads to the secretion of neurotrans- channel allows the larger potassium ions (radius 1.35 A)
8
−1
mitter. Typically, the neurotransmitter diffuses across the to move through the channel at 10 ions sec , which
synaptic cleft, over a distance of 20–40 nm, and binds to approaches the diffusion-limited rate, but essentially pre-
the neurotransmitter receptors on the adjacent cell. Thus vents smaller sodium ions (radius 0.95 A) to pass. It has
the signal is transmitted between the ∼10 12 cells of the been estimated that K + ions move through this chan-
mammalian nervous system. nel at least 10,000 times faster than sodium ions. The
˚
ion pore is about 45 A long. Three cation-binding sites
have been identified in it, two within a selectivity filter
˚
VI. PROPERTIES OF THE PROTEIN and separated by about 7.5 A and one in the cavity of
(POTASSIUM CHANNEL) THAT the pore (Fig. 7). Both the concentration gradient and the
+ +
+ +
ALLOWS K BUT NOT Na TO CROSS electromotive force provide the driving force moving the
THE MEMBRANE ions through the channel. To pass through the channel,
the inorganic ions have to pass through a selectivity fil-
Recently, we have learned some of the properties of one ter. The theory is that ions that enter the selectivity filter
channel that plays a central role in rapid signal transmis- must be dehydrated and that interaction of the dehydrated
sion. The K channel from bacteria was crystallized, af- K with carbonyl oxygens from amino-acid residues in-
+
+
ter a cytoplasmic tail of 33 residues was removed, and side the filter compensates for the dehydration. The dis-
MacKinnon and colleagues have determined its structure tances between the carboxyl oxygens of the protein and
at a resolution of 3.2 A (Fig. 7). This work represents two potassium ions in the filter are optimal to compen-
the first high-resolution, X-ray diffraction study of an ion- sate for the cost of dehydration of potassium ions, but
selective channel. Although the structure was obtained they would not be optimal for the dehydration of sodium
+
with the bacterial channel, K channels with similar se- ions.