A new class of scorpion toxin binding sites related to an A-type K+ channel: pharmacological characterization and localization in rat brain.

A new scorpion toxin (3751.8 Da) was isolated from the Buthus martensi venom, sequenced and chemically synthesized (sBmTX3). The A-type current of striatum neurons in culture completely disappeared when 1 microM sBmTX3 was applied (Kd=54 nM), whereas the sustained K+ current was unaffected. 125I-sBmTX3 specifically bound to rat brain synaptosomes (maximum binding=14 fmol x mg(-1) of protein, Kd=0.21 nM). A panel of toxins yet described as specific ligands for K+ channels were unable to compete with 125I-sBmTX3. A high density of 125I-sBmTX3 binding sites was found in the striatum, hippocampus, superior colliculus, and cerebellum in the adult rat brain.

Apamin improves reference memory but not procedural memory in rats by blocking small conductance Ca(2+)-activated K(+) channels in an olfactory discrimination task.

Apamin blocks SK channels responsible for long-lasting hyperpolarization following the action potential. Using an olfactory associative task, the effect of an intracerebroventricular 0.3 ng apamin injection was tested on learning and memory. Apamin did not modify the learning of the procedure side of the task or the learning of the odor-reward association. To test reference memory specifically, the rats were trained on a new odor-association problem using the same procedure (acquisition session), and they were tested for retention 24 h later. Apamin injected before or after the acquisition session improved retention of the valence of a new odor pair. Apamin injected before the retention session did not affect the retrieval of the new valence. Thus, the results indicate that the blockage of apamin-sensitive SK channels facilitate consolidation on new-odor-reward association.

Kaliotoxin, a Kv1.1 and Kv1.3 channel blocker, improves associative learning in rats.

Olfactory associative learning was used to investigate the involvement of Kv channels containing Kv1.1 and Kv1.3 alpha-subunits in learning and memory. Kaliotoxin (KTX), a specific inhibitor of these Kv channels, was injected intracerebroventricularly in the rat brain, at a dose of 10 ng that did not disturb the rats' locomotor activity or drinking behaviour. In the first paradigm (odour-reward training), KTX improved learning but not information consolidation. Moreover, KTX increased the long-term retrieval of an odour-reward association tested by a reversal test 1 month after the odour-reward training. The second paradigm (successive odour-pair training) tested reference memory. The first session was an acquisition session where the rats learned a new odour-discrimination problem with the same procedure. The second was a retention session held 24 h later to test retrieval of the learned information. KTX injected before the acquisition or retention session improved performance, but no effect was found when KTX was injected immediately after acquisition. We showed that these effects were not due to the action of KTX on attention processes. Thus, these results suggest that the blockage of Kv1.1 or Kv1.3 channels by KTX facilitates cognitive processes as learning, in particular in a reference representation.