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The most common inherited
disease in Caucasians is also an ion channel mutation.
2.
3.
Some forms of maturity-onset diabetes of the
young (MODY) may be attributed to such a mechanism.
4.
5.
Finally, a number of ion channels are secreted by
cells as toxic agents.
In many cases, genetic analysis of a
BOX 6.4
ION CHANNELS AND DISEASE
II.
CELLULAR AND MOLECULAR NEUROSCIENCE
disease has led to the cloning of the relevant ion channel.
Mutations in many different types of ion channels
have been shown to cause human diseases.
The list
increases daily.
6.9).
The a subunit of the Na+ channel contains four
internal repetitions (Fig.
6.9B).
Rather, inactivation is
triggered or facilitated as a secondary consequence
of activation.
MEMBRANE POTENTIAL AND ACTION POTENTIAL
II.
The a subunit has receptor sites for a-scorpion toxins (ScTX) and tetrodotoxin (TTX).
Cylinders represent probable
transmembrane a-helices.
The
assumption, therefore, was that the complicated pat-
II.
6.10).
The more prolonged the depolarization of
these cells, the more prolonged their discharge.
Examples of
cells that discharge in this manner are cortical and hip-
pocampal pyramidal cells.
6.10).
6.10) including some types of interneurons in the
cerebral cortex, thalamus, and hippocampus.
6.7 and 6.12).
Each type of ionic
ACTION POTENTIAL 125
126 6.
MEMBRANE POTENTIAL AND ACTION POTENTIAL
II.
II.
6.11).
6.10C).
6.11).
Other K+ currents activate with depolarization but also
inactivate with time.
6.12).
These K+ currents collectively are
referred to as IKCa (Fig.
6.11).
6.11).
ACTION POTENTIAL 127
128 6.
MEMBRANE POTENTIAL AND ACTION POTENTIAL
II.
6.11 and 6.12D).
Addition of IC (B) enhances action
potential repolarization.
Addition of IA (C) delays the onset of action potential generation.
Addition of IM (D) decreases the ability of the cell
to generate a train of action potentials.
Addition of IAHP (E) slows the fi ring rate and generates a slow after-hyperpolarization.
From
Huguenard and McCormick (1994).
II.
6.12D).
These channels are special in that they serve
two important functions.
6.11A.
6.11A).
This type of calcium
channel activates at relatively high thresholds and
does not inactivate.
6.10C;
Llinás, 1988).
6.10 and 6.12).
ACTION POTENTIAL 129
130 6.
MEMBRANE POTENTIAL AND ACTION POTENTIAL
II.
6.11A) often take
part in the generation of rhythmic bursts of action
potentials (Figs.
6.10 and 6.12).
This current inactivates with
maintained depolarization.
6.10).
6.13).
The low-threshold Ca2+ current
is inactivated and therefore the burst discharges are