Abstract
It has recently been proposed that the Ca$^2+$ uptake by the SR
is inhibited by blocking Cl$^-$ and/or K$^+$ movements across
this intracellular membrane. We have characterised the functional
and pharmacological profile of the SR K$^+$ channel derived from
human and sheep atrial cells. Mammalian atrial SR preparations were
subjected to (3)H-ryanodine binding assays, SDS-PAGE analysis
and channel protein reconstitution into planar lipid bilayers. Assessment
of (3)H-ryanodine binding on the SR Ca$^2+$ release channel
revealed that it was inhibited by both Ruthenium Red and Mg$^2+$
with IC(50) values of 4.11 microM and 9.12 m M, respectively. In
crude populations as well as in all SR-enriched fractions, activity
of K$^+$ selective channels was recorded. This channel displayed
a high conductance value of 193 and 185 pS for human and sheep preparations
respectively. Gating and conducting behaviours of this channel were
unaffected by the addition of up to 5m M 4-Aminopyridine (4-AP),
100 n M Iberiotoxin (IbTX), 10 microM E-4031 and 30 microM amiodarone.
However, 100n M Dendrotoxin (gamma-DTX) largely increase the occurrence
of the SR K$^+$ channel subconducting states without an effect
on the main unitary conductance. These results demonstrate that the
SR K$^+$ channel, present in all mammalian atrial SR membranes
tested (as assessed by (3)H-ryanodine binding and its typical inhibition
by ruthenium red and the magnesium), displays different properties
than those classically described for cardiac sarcolemmal K$^+$
channels. Despite the fact that the biophysical properties of the
SR K$^+$ channel are well known, its molecular identity remains
to be ascertained.
- 12392890
- animals,
- atria,
- cardiac,
- channel
- channels,
- child,
- conductivity,
- elapid
- electric
- gating,
- gov't,
- heart
- humans,
- ion
- magnesium,
- myocytes,
- non-u.s.
- potassium
- red,
- research
- reticulum,
- ruthenium
- ryanodine,
- sarcoplasmic
- sheep,
- support,
- venoms,
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