We have studied the ability of the calcium channel antagonist diltiazem to inhibit and reverse the porcine malignant hyperpyrexia (MH) syndrome. Pretreatment with diltiazem modified an MH response. Treatment with diltiazem was partially effective against a mild (or early) MH response. Diltiazem should not be considered to be an effective therapeutic agent for MH and should not displace the use ...

Whole-cell patch-clamp recordings were used to examine the regulation of voltage-dependent calcium channels by mu- and kappa-opioid receptors in acutely isolated rat dorsal root ganglion (DRG) sensory neurons. Agonists selective for either mu- (Tyr-Pro-NMePhe-D-Pro-NH2, PLO17) or kappa-opioid receptors (dynorphin A, U69,593) inhibited high-threshold calcium currents in a reversible and naloxone...

Whole cell currents and miniature glutamatergic synaptic events (minis) were recorded in vitro from cardiac vagal neurons in the nucleus ambiguus using the patch-clamp technique. We examined whether voltage-dependent calcium channels were involved in the nicotinic excitation of cardiac vagal neurons. Nicotine evoked an inward current, increase in mini amplitude, and increase in mini frequency i...

BACKGROUND Growth arrest and DNA-damage-inducible protein 45β reactivates methylation-silenced neural plasticity-associated genes through DNA demethylation. However, growth arrest and DNA-damage-inducible protein 45β-dependent demethylation contributes to neuropathic allodynia-associated spinal plasticity remains unclear. METHODS Adult male Sprague-Dawley rats (654 out of 659) received a spin...

Studies have shown that a combined application of several ion channel inhibitors immediately after central nervous system injury can inhibit secondary degeneration. However, for clinical use, it is necessary to determine how long after injury the combined treatment of several ion channel inhibitors can be delayed and efficacy maintained. In this study, we delivered Ca2+ entry-inhibiting P2X7 re...

Several haloperidol derivatives with a piperidine scaffold that was decorated at the nitrogen atom with different alkyl, benzyl, or substituted benzyl moieties were synthesized at our laboratory to establish a library of compounds with vasodilator activity. Compounds were screened for vasodilatory activity on isolated thoracic aorta rings from rats, and their quantitative structure-activity rel...

Ouabain increases atrial natriuretic peptide (ANP) secretion. When isolated superfused rat left atria were paced at 2 Hz, ouabain at concentrations of 50, 100, and 200 microM increased ANP secretion by 2.0 +/- 0.3-, 3.2 +/- 0.5-, and 4.2 +/- 0.5-fold, respectively. In this study, we examine the mechanism of ouabain-stimulated ANP secretion using the dose of 100 microM. To determine whether calc...

The primary mode of action of local anesthetics is through sodium channel and axonal conduction blockade. Local anesthetics have also extensive effects on pre-synaptic calcium channels that must function to stimulate the release of neurotransmitters. Thus, interference with calcium channel conductance may enhance spinal anesthesia with local anesthetics. The present study was designed to invest...

The primary mode of action of local anesthetics is through sodium channel and axonal conduction blockade. Local anesthetics have also extensive effects on pre-synaptic calcium channels that must function to stimulate the release of neurotransmitters. Thus, interference with calcium channel conductance may enhance spinal anesthesia with local anesthetics. The present study was designed to invest...