Sympathetic hyperactivity and parasympathetic insufficiency characterize blood pressure (BP) control in genetic hypertension. This shift is difficult to investigate in anesthetized rats. Here we present a pharmacological approach to simultaneously provoke sympathetic and parasympathetic transmitter release, and identify their respective roles in the concomitant cardiovascular response. To stimu...

Background and purpose: Progressive degeneration of dopaminergic neurons in the midbrain is the main mechanism of Parkinson’s disease (PD). Although potassium channels affect neural activity and death in this area, little research has investigated the effect of potassium channel blockers, such as 4-aminopyridine in the pretreatment of PD. Methods: Fifty-six healthy male Wistar rats were selecte...

A-type potassium current (I(A)) both activates and inactivates at subthreshold voltages. We asked whether there is steady-state I(A) at subthreshold voltages, using dissociated mouse tuberomammillary nucleus neurons, pacemaking neurons with large I(A) currents in which subthreshold I(A) might regulate firing frequency. With slow depolarizing voltage ramps (20 mV/s), there was no discernible com...

A new drug, 4-aminopyridine, was prepared for use in humans and tested by repeated injections in six patients with myasthenia gravis. The drug caused improvement of muscle strength and neuromuscular transmission as demonstrated by clinical observations and repetitive electrical nerve stimulation. The drug was effective in cases without any other treatment as well as in cases undergoing treatmen...

The mechanism by which 4-aminopyridine (4-AP) blocks the delayed rectifier type potassium (K+) channels present on lipopolysaccharide-activated murine B lymphocytes was investigated using whole-cell and single channel patch-clamp recordings. 4-AP (1 microM-5 mM) was superfused for 3-4 min before applying depolarizing pulses to activate the channel. During the first pulse after application of 4-...

Downbeat nystagmus (DBN), the most common form of acquired fixation nystagmus, is often caused by cerebellar degeneration, especially if the vestibulo-cerebellum is involved. The upward ocular drift in DBN has a spontaneous and a vertical gaze-evoked component. Since cerebellar involvement is suspected to be the underlying pathomechanism of DBN, we tested in 15 patients with DBN whether the app...

Neurons adapt to seizure activity structurally and functionally to attenuate hyperactive neural circuits. Homer proteins provide a scaffold in the postsynaptic density (PSD) by binding to ligands through an EVH1 domain and to other Homer proteins by a coiled-coil domain. The short Homer isoform 1a (H1a) has a ligand-binding domain but lacks a coiled-coil domain and thus acts in a dominant-negat...