Abstract
The effects of aminopyridine analogs in Ca2+-activated K+ channels in GH3 clonal anterior pituitary cells were studied using whole-cell voltage-clamp and single-channel recording techniques. Step depolarization from a holding potential of -50 mV activated a noninactivating, tetraethylammonium- and Cd2+-sensitive outward current. Tail current analysis indicated that this sustained outward current is carried predominantly by K+ ions. Extracellular perfusion with 4-aminopyridine and 3,4-diaminopyridine (0.05-5 mM) caused a dose-dependent enhancement of the outward current by up to 100 and 170%, respectively. This effect typically occurred with prolonged depolarizations of >1-2 sec. Patch-clamp recordings in the cell-attached configuration demonstrated that 4-aminopyridine (2 mM) promotes the activity of a large-conductance (150-175 pS; 50-135 mM external K+), tetraethylammonium-sensitive, Ca2+-activated K+ channel; the drug had no effect on these channels in excised patches. These results indicate that aminopyridines enhance the opening of Ca2+-activated K+ channels in GH3 cells. Several lines of evidence suggest that this effect may occur indirecty, possibly as a result of an increase in the effective intracellular free Ca2+ level.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 458-468 |
| Number of pages | 11 |
| Journal | Molecular Pharmacology |
| Volume | 35 |
| Issue number | 4 |
| State | Published - 1989 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Pharmacology
Cite this
Aminopyridines enhance opening of calcium-activated potassium channels in GH3 anterior pituitary cells. / Rogawski, Michael A.
In: Molecular Pharmacology, Vol. 35, No. 4, 1989, p. 458-468.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Aminopyridines enhance opening of calcium-activated potassium channels in GH3 anterior pituitary cells
AU - Rogawski, Michael A
PY - 1989
Y1 - 1989
N2 - The effects of aminopyridine analogs in Ca2+-activated K+ channels in GH3 clonal anterior pituitary cells were studied using whole-cell voltage-clamp and single-channel recording techniques. Step depolarization from a holding potential of -50 mV activated a noninactivating, tetraethylammonium- and Cd2+-sensitive outward current. Tail current analysis indicated that this sustained outward current is carried predominantly by K+ ions. Extracellular perfusion with 4-aminopyridine and 3,4-diaminopyridine (0.05-5 mM) caused a dose-dependent enhancement of the outward current by up to 100 and 170%, respectively. This effect typically occurred with prolonged depolarizations of >1-2 sec. Patch-clamp recordings in the cell-attached configuration demonstrated that 4-aminopyridine (2 mM) promotes the activity of a large-conductance (150-175 pS; 50-135 mM external K+), tetraethylammonium-sensitive, Ca2+-activated K+ channel; the drug had no effect on these channels in excised patches. These results indicate that aminopyridines enhance the opening of Ca2+-activated K+ channels in GH3 cells. Several lines of evidence suggest that this effect may occur indirecty, possibly as a result of an increase in the effective intracellular free Ca2+ level.
AB - The effects of aminopyridine analogs in Ca2+-activated K+ channels in GH3 clonal anterior pituitary cells were studied using whole-cell voltage-clamp and single-channel recording techniques. Step depolarization from a holding potential of -50 mV activated a noninactivating, tetraethylammonium- and Cd2+-sensitive outward current. Tail current analysis indicated that this sustained outward current is carried predominantly by K+ ions. Extracellular perfusion with 4-aminopyridine and 3,4-diaminopyridine (0.05-5 mM) caused a dose-dependent enhancement of the outward current by up to 100 and 170%, respectively. This effect typically occurred with prolonged depolarizations of >1-2 sec. Patch-clamp recordings in the cell-attached configuration demonstrated that 4-aminopyridine (2 mM) promotes the activity of a large-conductance (150-175 pS; 50-135 mM external K+), tetraethylammonium-sensitive, Ca2+-activated K+ channel; the drug had no effect on these channels in excised patches. These results indicate that aminopyridines enhance the opening of Ca2+-activated K+ channels in GH3 cells. Several lines of evidence suggest that this effect may occur indirecty, possibly as a result of an increase in the effective intracellular free Ca2+ level.
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UR - http://www.scopus.com/inward/citedby.url?scp=0024508531&partnerID=8YFLogxK
M3 - Article
C2 - 2704369
AN - SCOPUS:0024508531
VL - 35
SP - 458
EP - 468
JO - Molecular Pharmacology
JF - Molecular Pharmacology
SN - 0026-895X
IS - 4
ER -