Humans with the disorder episodic ataxia type 2 (EA2) and the tottering mouse mutant exhibit episodic attacks induced by emotional and chemical stress. Both the human and mouse disorders result from mutations in CACNA1A, the gene encoding the alpha(1)2.1 subunit of Ca(v)2.1 voltage-gated calcium channels. These mutations predict reduced calcium currents, particularly in cerebellar Purkinje cell...

The effects of some cholinergic agents and 4-aminopyridine (4-AP) on neurally mediated contractions of in vitro cat ciliary muscle preparations were studied. The contractile response to trains of stimuli was enhanced by eserine and completely blocked by tetrodotoxin or atropine. Low concentrations of carbachol did not modify muscle resting tension but clearly attenuated contractile response to ...

BACKGROUND The ultrarapid outward current I(Kur) is a major repolarizing current in human atrium and a potential target for treating atrial arrhythmias. The effects of selective block of I(Kur) by low concentrations of 4-aminopyridine or the biphenyl derivative AVE 0118 were investigated on right atrial action potentials (APs) in trabeculae from patients in sinus rhythm (SR) or chronic atrial f...

We have studied the effects of the potassium-blocking agent 4-aminopyridine (4-AP) on the action potential and membrane currents of the sheep cardiac Purkinje fiber. 4-AP slowed the rate of phase 1 repolarization and shifted the plateau of the action potential to less negative potentials. In the presence of 4-AP, the substitution of sodium methylsulfate or methanesulfonate for the NaCl of Tyrod...

Previous studies suggest that aminopyridine may play a role in the symptomatic treatment of fatigue in multiple sclerosis. Although the mechanism underlying the beneficial effect on fatigue remains unclear, it has been proposed that aminopyridines may help to improve conduction in demyelinated central pathways, implicating both axonal and synaptic mechanisms. The objective of the present study ...

Aminopyridines (2-AP, 3-AP, and 4-AP) selectively block K channels of squid axon membranes in a manner dependent upon the membrane potential and the duration and frequency of voltage clamp pulses. They are effective when applied to either the internal or the external membrane surface. The steady-state block of K channels by aminopyridines is more complete for low depolarizations, and is gradual...

Effects of 4-aminopyridine (4-AP) and tetraethylammonium (TEA) on vasodilator actions of 2-nicotinamidoethyl nitrate (SG-75) were investigated using isolated dog coronary arteries. SG-75 10(-8)--10(-4) Gm/ml produced concentration-dependent relaxations of coronary arterial strips which were contracted with potassium 30 mM or prostaglandin (PG) F2 alpha 10(-6) Gm/ml. Both 4-AP 5 x 10(-4) Gm/ml a...

Aminopyridines such as 4-aminopyridine (4AP) are widely used as voltage-activated K+ (Kv) channel blockers and can improve neuromuscular function in patients with spinal cord injury, myasthenia gravis, or multiple sclerosis. Here we present novel evidence that 4AP and several of its analogues directly stimulate high voltage-activated Ca2+ channels (HVACCs) in native neurons. 4-AP, 4( a m i n o ...

Episodic ataxia type 2 (EA2) is a hereditary cerebellar ataxia associated with mutations in the P/Q-type voltage-gated calcium (Ca(2+)) channels. Therapeutic approaches for treatment of EA2 are very limited. Presently, the potassium (K(+)) channel blocker 4-aminopyridine (4-AP) constitutes the most promising treatment, although its mechanism of action is not understood. Here we show that, in co...

The molecular identity of vascular delayed rectifier K(+) channels (K(DR)) is poorly characterized. Inhibition by 4-aminopyridine (4-AP) of K(DR) of rabbit portal vein (RPV) myocytes was studied by patch clamp and compared with that of channels composed of Kv1.5 and/or Kv1.2 subunits cloned from the RPV and expressed in mammalian cells. 4-AP block of K(DR) was pulse-frequency dependent, require...