Laboratory of Synthetic Genome Biology
Developing biological engineering approaches to understand epigenetics and genome organization in C. elegans

Grunnet et al. (2001) Neuropharmacology

Pharmacological modulation of SK3 channels

Grunnet et al. (2001). Pharmacological modulation of SK3 channels. ​Neuropharmacology.​​​
Morten Grunnet, Thomas Jespersen, Kamilla Angelo, Christian Frøkjær-Jensen, Dan A Klaerke, Søren-Peter Olesen, Bo Skaaning Jensen
SK channel, afterhyperpolarization, pharmacology, Olesen Lab, University of Copenhagen
2001
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).