Biology Reference
In-Depth Information
A review of contemporary molecular models of various ion channels capable
of supporting action potentials suggests that H and H happened on a most
remarkable level of abstraction/aggregation that would support very broad gen-
eralization in terms of the specificity of membrane currents, though not any
specific molecular mechanisms. For example, the chapter by Koester and Siegel-
baum on 'Propagated Signaling: The Action Potential' in Kandel et al. (2000)
states somewhat 'teleologically' that
The squid axon can generate an action potential with just two types of voltage-
gated channels. Why then are there so many
different types
of voltage-gated chan-
nels found in the nervous system? The answer is that neurons with the expanded
set of voltage-gated channels have much more complex information-processing
abilities than those with only two types of channels.
(p. 159) (my emphasis)
The number and types of ion channels are explained, and to an extent unified,
by the underlying genetics (and epigenetics) of ion channel diversity, a topic to
which I turn next.
3.2. Genetic and epigenetic diversity accounts for ion channel diversity
Hille recounts the history of ion channel research over the course of the last
half-century following H and H's classic paper. The progress he writes has been
'phenomenal', and 'the field has become highly interdisciplinary, combining
approaches of biophysics, pharmacology, protein chemistry, molecular and med-
ical genetics, and cell biology' (Hille, 2001, p. 61). Several recent Nobel prizes
have, in point of fact, been awarded for ion channel research, including to Neher
and Sakmann in 1991, who developed the 'patch clamp method' that provided
direct evidence of ion channels, and to MacKinnon in 2003, for structural and
mechanistic studies of ion channels, including his pore model.
Genetic studies that began in the 1980s have indicated that there are three
general genetic 'superfamilies' of ion channels, comprising ligand-gated, gap-
junction, and the H and H type of action potential generating voltage gated
channels. This last class, which is activated by depolarization, also contains three
subclasses of channels selective for Na
+
, and K
+
Ca
2
+
(Siegelbaum & Koester,
2000). Siegelbaum & Koester describe the similar architecture of this class of
channels writing:
They contain four repeats of a basic motif composed of six transmembrane
segments [known as] (S1-S6). The S5 and S6 segments are connected by a
loop, through the extracellular face of the membrane, the P-region, that forms
the selectivity filter of the channel. A single subunit of voltage gated Na
+
and
