The localization of the receptor for apamin, a specific toxin for one class of sensitive Ca2+-dependent K+ channel, was studied in rat brain using an in vitro autoradiographic technique. Radiolabeled monoiodoapamin binds specifically to rat brain sections with a high affinity (Kd = 25 pM) to a single class of sites. Autoradiograms demonstrated a very heterogeneous distribution of the apamin rec...

Activity-dependent changes in neuronal excitability and synaptic strength are thought to underlie memory encoding. In hippocampal CA1 neurons, small conductance Ca2+-activated K+ (SK) channels contribute to the afterhyperpolarization, affecting neuronal excitability. In the present study, we examined the effect of apamin-sensitive SK channels on the induction of hippocampal synaptic plasticity ...

BACKGROUND The transmural distribution of apamin-sensitive small conductance Ca(2+)-activated K(+) (SK) current (IKAS) in failing human ventricles remains unclear. METHODS AND RESULTS We optically mapped left ventricular wedge preparations from 12 failing native hearts and 2 rejected cardiac allografts explanted during transplant surgery. We determined transmural action potential duration (AP...

The discharge patterns of respiratory neurons of the caudal ventral respiratory group (cVRG) appear to be subject to potent GABAergic gain modulation. Local application of the GABA(A) receptor antagonist bicuculline methochloride amplifies the underlying discharge frequency (F(n)) patterns mediated by endogenous excitatory and inhibitory synaptic inputs. Gain modulation can also be produced by ...

Miniprotein phage display screening yields structured peptides with high affinity for the Estrogen Receptor (ER). Hits from apamin phage libraries feature a LXXLL motif specifically placed on the predefined miniprotein helical segment. The apamin scaffold also allows optimization of flanking amino acids to ensure an optimal ER binding affinity.

In cirrhosis, in splanchnic arteries, endothelium-dependent relaxation may persist even if overactive nitric oxide synthase (NOS) and cyclooxygenase (COX) are inhibited. In normal arteries, a significant endothelium-dependent relaxation to acetylcholine persists after NOS/COX inhibition. This relaxation is caused by smooth muscle cell (SMC) membrane hyperpolarization, which is sensitive to a co...

BACKGROUND A secondary rise of intracellular Ca(2+) (Cai) and an upregulation of apamin-sensitive K(+) current (I(KAS)) are characteristic findings of failing ventricular myocytes. We hypothesize that apamin, a specific I(KAS) blocker, may induce torsades de pointes (TdP) ventricular arrhythmia from failing ventricles exhibiting secondary rises of Cai. OBJECTIVE To test the hypothesis that sm...

BACKGROUND Hypokalemia increases the vulnerability to ventricular fibrillation. We hypothesize that the apamin-sensitive small-conductance calcium-activated potassium current (IKAS) is activated during hypokalemia and that IKAS blockade is proarrhythmic. METHODS AND RESULTS Optical mapping was performed in 23 Langendorff-perfused rabbit ventricles with atrioventricular block and either right ...

Activation of small-conductance calcium (Ca(2+))-dependent potassium (K(Ca)2) channels (herein called "SK") produces membrane hyperpolarization to regulate membrane excitability. Three subtypes (SK1-3) have been cloned and are distributed throughout the nervous system, smooth muscle, and heart. It is difficult to discern the physiological role of individual channel subtypes as most blockers or ...

The hypoxia-evoked secretion of catecholamines from the noninnervated fetal adrenal gland is essential for surviving intrauterine hypoxemia. The ion channels responsible for the initial depolarization that leads to catecholamine secretion have not been identified. Patch-clamp studies of adrenal chromaffin cells isolated from fetal and adult sheep revealed the presence of a Ca(2+)-dependent K(+)...