Abstract
The nature of open state block was characterized in isolated canine
cardiac sarcoplasmic reticulum (SR) potassium channel incorporated
into planar lipid bilayers. 4-Aminopyridine (4-AP) blocked the open
conductance state of the potassium channels in a voltage-dependent
manner. Blockade was reversible, occurred from either the cis (cytoplasmic)
or the trans (lumenal) side and was competitive with potassium ions.
Reversal potential measurements indicated that this channel was impermeable
to 4-AP. Measured effective electrical distances were roughly symmetrical
and indicated penetration of 0.39 and 0.42 of the membrane electrical
field from the cis and trans sides, respectively. Effective electrical
distance was insensitive to potassium ion concentration in the range
50 to 200 mM and indicated that 4-AP was able to penetrate relatively
deeply into the pore compared with blockade of sarcolemmal potassium
channels. Potassium ion concentration and voltage dependence of 4-AP
blockade were consistent with a two binding site blockade model,
similar to the model used previously to describe calcium ion blockade
of the SR potassium ion channel. Unlike calcium blockade, however,
4-AP blocked from either cis or trans in a similar manner, suggesting
a distinct binding site for each of these two blockers. Open channel,
voltage-dependent blockade of the SR potassium channel by 4-AP is
in marked contrast to its action on sarcolemmal potassium channels
and suggests that either 4-AP penetrates much farther into the potassium
channel permeation pathway than was previously believed, or the SR
potassium channel has a very different physical pore arrangement
from that of sarcolemmal potassium channels.
- 4-aminopyridine,
- 9520865
- agments,
- allosteric
- animals,
- binding,
- channel
- channels,
- dogs,
- fr,
- gating,
- heart,
- humans,
- ion
- membrane
- myocardium,
- peptide
- potassium
- potentials,
- protein
- regulation,
- reticulum,
- sarcoplasmic
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