Pharmacological modulation of SK3 channels
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Pharmacological modulation of SK3 channels. / Grunnet, M; Jespersen, Thomas; Angelo, K; Frøkjaer-Jensen, C; Klaerke, D A; Olesen, S P; Jensen, B S.
In: Neuropharmacology, Vol. 40, No. 7, 01.06.2001, p. 879-887.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Pharmacological modulation of SK3 channels
AU - Grunnet, M
AU - Jespersen, Thomas
AU - Angelo, K
AU - Frøkjaer-Jensen, C
AU - Klaerke, D A
AU - Olesen, S P
AU - Jensen, B S
PY - 2001/6/1
Y1 - 2001/6/1
N2 - Small-conductance, calcium-activated K+ channels (SK channels) are voltage-insensitive channels that have been identified molecularly within the last few years. As SK channels play a fundamental role in most excitable cells and participate in afterhyperpolarization (AHP) and spike-frequency adaptation, pharmacological modulation of SK channels may be of significant clinical importance. Here we report the functional expression of SK3 in HEK293 and demonstrate a broad pharmacological profile for these channels. Brain slice studies commonly employ 4-aminopyridine (4-AP) to block voltage-dependent K+ channels or a methyl derivative of bicuculline, a blocker of gamma-aminobutyric acid (GABA)-gated Cl- channels, in order to investigate the role of various synapses in specialized neural networks. However, in this study both 4-AP and bicuculline are shown to inhibit SK3 channels (IC50 values of 512 microM and 6 microM, respectively) at concentrations lower than those used for brain slice recordings. Riluzole, a potent neuroprotective drug with anti-ischemic, anticonvulsant and sedative effects currently used in the treatment of amyotrophic lateral sclerosis, activates SK3 channels at concentrations of 3 microM and above. Amitriptyline, a tricyclic antidepressive widely used clinically, inhibits SK3 channels with an IC50 of 39.1 +/- 10 microM (n=6).
AB - Small-conductance, calcium-activated K+ channels (SK channels) are voltage-insensitive channels that have been identified molecularly within the last few years. As SK channels play a fundamental role in most excitable cells and participate in afterhyperpolarization (AHP) and spike-frequency adaptation, pharmacological modulation of SK channels may be of significant clinical importance. Here we report the functional expression of SK3 in HEK293 and demonstrate a broad pharmacological profile for these channels. Brain slice studies commonly employ 4-aminopyridine (4-AP) to block voltage-dependent K+ channels or a methyl derivative of bicuculline, a blocker of gamma-aminobutyric acid (GABA)-gated Cl- channels, in order to investigate the role of various synapses in specialized neural networks. However, in this study both 4-AP and bicuculline are shown to inhibit SK3 channels (IC50 values of 512 microM and 6 microM, respectively) at concentrations lower than those used for brain slice recordings. Riluzole, a potent neuroprotective drug with anti-ischemic, anticonvulsant and sedative effects currently used in the treatment of amyotrophic lateral sclerosis, activates SK3 channels at concentrations of 3 microM and above. Amitriptyline, a tricyclic antidepressive widely used clinically, inhibits SK3 channels with an IC50 of 39.1 +/- 10 microM (n=6).
KW - 4-Aminopyridine
KW - Amitriptyline
KW - Animals
KW - Antidepressive Agents, Tricyclic
KW - Apamin
KW - Bicuculline
KW - Cell Line
KW - Humans
KW - Neuroprotective Agents
KW - Potassium Channels
KW - Potassium Channels, Calcium-Activated
KW - Rats
KW - Riluzole
KW - Small-Conductance Calcium-Activated Potassium Channels
M3 - Journal article
C2 - 11378158
VL - 40
SP - 879
EP - 887
JO - Neuropharmacology
JF - Neuropharmacology
SN - 0028-3908
IS - 7
ER -
ID: 165644