New High-Affinity Peptide Ligands for Kv1.2 Channel: Selective Blockers and Fluorescent Probes.

Advanced molecular probes are required to study the functional activity of the Kv1.2 potassium channel in normal and pathological conditions. To address this, a fully active Kv1.

Non-conventional toxin WTX and its disulfide-fixed synthetic fragments: Interaction with nicotinic acetylcholine receptors and reduction of blood pressure.

Non-conventional snake venom toxins, such as WTX from the cobra Naja kaouthia, are three-finger proteins containing a fifth disulfide bond in the N-terminal polypeptide loop I and inhibiting α7 and muscle-type nicotinic acetylcholine receptors (nAChRs). Because the central polypeptide loop II of non-conventional toxins plays an important role in their biological activity, we synthesized several WTX loop II fragments with two cysteine residues added at the N- and C-termini and oxidized to form a disulfide bond. The inhibition by peptides of several nAChRs subtypes was investigated using different methods and the effects of peptides on the rat arterial pressure and heart rate were analyzed.

Inhibition of nicotinic acetylcholine receptors by oligoarginine peptides and polyamine-related compounds.

Oligoarginine peptides, known mostly for their cell-penetrating properties, are also inhibitors of the nicotinic acetylcholine receptors (nAChRs). Since octa-arginine (R8) inhibits α9α10 nAChR and suppresses neuropathic pain, we checked if other polycationic compounds containing amino and/or guanidino groups could be effective and tested the activity of the disulfide-fixed "cyclo"R8, a series of biogenic polyamines (putrescine, spermidine, and spermine), -methylated spermine analogs, agmatine and its analogs, as well as acylpolyamine argiotoxin-636 from spider venom. Their inhibitory potency on muscle-type, α7 and α9α10 nAChRs was determined using radioligand analysis, electrophysiology, and calcium imaging.

Anti-smoking drugs cytisine and varenicline reduce cardiac reperfusion injury in rat model of myocardial ischemia.

Evidence to date indicates that activation of nicotinic acetylcholine receptors (nAChRs) can reduce cardiac injury from ischemia and subsequent reperfusion. The use of nAChR agonists in various animal models leads to a reduction in reperfusion injury. Earlier this effect was shown for the agonists of α7 nAChR subtype.

Interactions of the Kv1.1 Channel with Peptide Pore Blockers: A Fluorescent Analysis on Mammalian Cells.

The voltage-gated potassium channel Kv1.1, which is abundant in the CNS and peripheral nervous system, controls neuronal excitability and neuromuscular transmission and mediates a number of physiological functions in non-excitable cells. The development of some diseases is accompanied by changes in the expression level and/or activity of the channels in particular types of cells.