Towards Therapeutic Applications of Arthropod Venom K+-Channel Blockers in CNS Neurologic Diseases Involving Memory Acquisition and Storage

Table 2

K⁺ channels manipulations and their effects on experimental behavioral models for learning and memory.

Channels	Technique	Effect on channel	Behavioral test	Result	Ref.
Kv, KCa, and Kir	icv of minoxidil, pinacidil, TEA, glibenclamine, gliquidone, and cromakalim.	TEA blocks Kv and KCa. Gliquidone and glibenclamide block Kir. Minoxidil, pinacidil and cromakalim open Kir	PAT in mice	Minoxidil, pinacidil and cromakalim: (−); TEA, glibenclamine, gliquidone: (+)	[50]
Kv1.1	icv of antisense oligodeoxyribonucleotide to Kv1.1 mRNA.	Inhibition of channel expression	PAT in mice	(−)	[51]
			MWM in rats	(−)
Kv12.2	Kv12.2 (BEC1) knockout mice	Inhibition of channel expression	MWM	(+)
			Y-maze test	(+)
			WFT	(+)
	Kv12.2 OVER mice	Overexpression of channel in the forebrain	MWM	(−)	[52]
			Y-maze test	(−)
			WFT	(−)
KCa2	Systemic Infusion of EBIO or CyPPA.	EBIO activates SK channels. CyPPA activates KCa2.2 (SK2)/KCa2.3 (SK3) subunits over KCa2.1 (SK1), and is more potent than EBIO.	ORT in mice	EBIO: (−); CyPPA: (−)
			Contextual FCP in mice	EBIO: (0); CyPPA: (NT)	[53]
			Tone FCP in mice	EBIO: (0); CyPPA: (NT)
KCa1.1	ih (CA1) of paxilline	Paxilline blocks the channel.	Trace eyeblink in rats	(−)	[54]
KCa2.2	SK2-OVER mice	Overexpression of KCa2.2 (SK2) protein and KCa2.2 mRNA	MWM	(−)
			Contextual FCP	(−)	[55]
			Tone FCP	(−)
KCa2.2	SK2-OVER mice	Overexpression of KCa2.2 (SK2) protein and KCa2.2 mRNA	Contextual FCP	(−)	[56]
KCa2.3	Doxycycline-induced conditional SK3 channel deficient (T/T) mice	Inhibition of channel expression	PAT	(0)
			MWM	(0)
			ORT	(0)
			Y-maze test	(−)	[57]
			Five-trial inhibitory avoidance test	(−)
K2P10.1	Infusion of siRNA in the EC.	Knock down K2p10.1 channels in the EC.	MWM in rats	(+)	[58]
Kir3.4	Kir3.4 (GIRK4) knockout mice	Inhibition of channel expression	PAT	(0)	[51]
			MWM	(−)
Kir6.2	ih (CA3) of diazoxide, or tolbutamide, or both.	Diazoxide opens the channel. Tolbutamide blocks the channel.	Contextual FCP in mice	Diazoxide: (−) Tolbutamide: (0) Both: (0)	[48]
			Tone FCP in mice	Diazoxide, tolbutamide or both: (0)
	Kir6.2 knockout mice	Inhibition of channel expression	Contextual FCP	(−)
			Tone FCP	(−)
			MWM	(0/−)

(−): impairment; (+): improved; (0): neutral; (0/−): slight impairment; (NT): not tested; Ref.: reference; icv: intracerebroventricular injection; ih: intra-hippocampal injection; EC: entorhinal cortex; OVER: overexpressing; EBIO: 1-ethyl-2-benzimidazolinone; CyPPA: Cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine; siRNA: small interfering RNA; PAT is used for passive-avoidance test; MWM for Morris water maze test; WFT for Water-finding task; ORT for object recognition task; FCP for fear-conditioning paradigm.