Effects of verapamil on the release of different neurotransmitters

The effect of verapamil on resting and depolarization-induced monoamine release was investigated in rat hippocampal synaptosomes prelabeled with [³H]-5-hydroxytryptamine (HT) or [³H]-norepinephrine (NE) and rat striatal synaptosomes prelabeled with [³H]-dopamine (DA). Verapamil (50 μM) completely abolishes high K⁺-induced [³H]-NE release, but paradoxically facilitates high K⁺-induced [³H]-5-HT and [³H]-DA release. All these high K⁺-evoked responses were Ca²⁺ dependent. Verapamil does not modify [³H]-NE baseline release, but increases dose dependently [³H]-5-HT and [³H]-DA baseline release. Verapamil (10 μM, for 5 min) increases endogenous DA release (70%) and endogenous 5-HT release (40%) independently on the presence of external Ca²⁺. The total amount of these monoamines (released plus retained by the preparation) and their metabolites (DOPAC and 5-HIAA) was similar in control and verapamil-treated synaptosomes. Verapamil displaces [³H]-spiroperidol specific binding (K_i of 2.4 × 10^?6M) and [³H]-SCH-23390 specific binding (K_i of 9 × 10^?6M) from striatal synaptosomal membranes, and [³H]-5-HT specific binding (K_i of 3 × 10^?5M) from hippocampal synaptosomal membranes. It is concluded that in addition to the Ca²⁺ antagonistic properties of verapamil on the Ca²⁺-dependent, depolarization-induced release of some neurotransmitters [gamma aminobutyric acid (GABA and NE)], another mechanism probably mediated by presynaptic receptors underlies the effects of verapamil on DA and 5-HT release from discrete brain regions. © 1995 Wiley-Liss, Inc.     

Synthetic peptides corresponding to the sequence of noxiustoxin indicate that the active site of this K+ channel blocker is located on its amino-terminal portion

Summary A nonapeptide Thr-Ile-Ile-Asn-Val-Lys-Cys-Thr-Ser (NTX_1–9) and a decapeptide Met-Asn-Gly-Lys-Cys-Lys-Cys-Tyr-Asn-Asn (NTX_30–39) corresponding to the N-terminal and C-terminal sequences respectively of Noxiustoxin (NTX) were synthesized by the solid phase method of Merrifield (1963). The first synthetic peptide (NTX_1–9) was shown to be toxic to mice independently of the route of administration: intraperitoneally, subcutaneously or intraventricularly (100–200 g/20 g mouse weight). The second (NTX_30–39) was not toxic even at higher dose (400 g/20 g mouse). When the effects of the peptide NTX_1–9 and of the authentic toxin (Noxiustoxin) were studied on the liberation of [³H] 4-aminobutyric acid (³H-GABA) from mouse synaptosomes, both gave essentially the same results, except that peptide NTX_1–9 was needed at higher concentration. Synthetic peptide NTX_30–39 had no effect in the same preparation at even higher doses. The GABA release produced by toxic peptide NTX_1–9 was not affected by tetrodotoxin but was completely abolished by the presence of the K⁺ ionophore valinomycin, mimicking the effect of native NTX in the same system (Sitges et al., 1986). These results indicate that the toxic active site of Noxiustoxin is possibly located in or near the N-terminal amino acid portion of the molecule.Abbreviations used BOC amino acids ter-butyloxycarbonyl-amino acids - BOC amino acid-PAM-resin ter-butyloxycarbonyl-aminoacyl-4-(oxymethyl)-phenacetamidomethyl-resin - GABA 4 aminobutyric acid - HPLC high performance liquid chromatography - MSA mouse serum albumin - NTX Noxiustoxin - NTX _(numbers) synthetic peptides with amino acid sequences of NTX at position start (first number) to position end (second number) of the sequence according to Fig. 1 - TTX tetrodotoxin Supported in part by the Mexican Council of Science and Technology (CONACyT), grants PVT/QF/NAL/84/2182, PVT/AI/NAL/85/3029 to L.D.P.; PCSACNA 022640 to A.B. A patent request claiming rights on the use of synthetic NTX and related peptides was presented in Washington, DC (U.S.A.), Serial number 07/132,169, filing date December 14, 1987.     

Simultaneous action of MK-801 (dizclopine) on dopamine, glutamate, aspartate and GABA release from striatum isolated nerve endings

The simultaneous effect of MK-801 on the baseline- and depolarization (20 microM veratridine or 30 mM high K+)-evoked release of endogenous dopamine, glutamate (Glu), aspartate (Asp), and GABA is investigated in the same preparation of rat striatum isolated nerve endings. MK-801, in the microM range, selectively increases the baseline and high K+ depolarization-evoked release of dopamine, without causing any effect on the baseline or on the high K+-evoked release of Glu, Asp and GABA. In addition to this selective action on dopamine release, MK-801 inhibits the veratridine depolarization-evoked release of all the neurotransmitters tested, including dopamine. In SBFI and fura-2 preloaded striatal synaptosomes, MK-801 inhibits the elevation of internal Na+ (Na(i)) and the elevation of internal Ca2+ (Ca(i)) induced by veratridine depolarization. The elevation of Ca(i) induced by high K+ depolarization is unchanged by MK-801. This study reveals two separate MK-801 actions. (1) The voltage-independent action, which increases dopamine release selectively, and might contribute to the effects of MK-801 on motor coordination. (2) The voltage-dependent action, which inhibits all the veratridine-evoked responses including the evoked release of the excitatory amino acids (which are particularly concentrated in striatum nerve endings), and might contribute to the anticonvulsant and neuroprotective effects of MK-801.     

Changes in mitral valve geometry after percutaneous valve repair with the MitraClip® System

The International Journal of Cardiovascular Imaging - The aim of our study was to assess the anatomical changes of the mitral valve apparatus after percutaneous repair with the MitraClip®...     

Ablation of frequent premature ventricular complex in an athlete

Premature ventricular complex are common findings in the exam of many athletes. There is no extensive scientific evidence in the management of this situation particularly when associated with borderline contractile function of the left ventricle. In this case report, we present a 35‐year‐old asymptomatic healthy athlete with high incidence (over 10 000 beats in 24 h) of premature ventricular complex and left ventricular dilatation with dysfunction, which persisted after a resting period of 6 months without training. We performed radiofrequency ablation of the premature ventricular complex focus. After 1‐year follow‐up, he was asymptomatic without arrhythmia and the left ventricle normalized its size and function as shown by echocardiogram and cardiac magnetic resonance.     

Improved outcomes and complications of atrial fibrillation catheter ablation over time: learning curve, techniques, and methodology

Introduction and objectives

The outcomes of atrial fibrillation ablation procedures vary widely between different centers. Our objective was to analyze the results and complications of this procedure in our center and identify factors predicting the efficacy and safety of atrial fibrillation ablation.

Methods

In total, 726 atrial fibrillation ablation procedures were performed in our center between 2002 and 2009. Beginning in January 2008, a protocol for anticoagulation and conscious sedation was systematically applied. Outcomes and complications could therefore be compared in 2 well-differentiated groups: group A included 419 procedures performed prior to 2008 and group B included 307 procedures completed after 2008 using the new protocol.

Results

During an average follow-up of 8.7 months, 60.9% of patients were arrhythmia-free after one or repeat procedures. After only 1 procedure, the success rate was 41% and significantly higher in group B (51.6% vs 35.2% in group A; P=.001). There were 31 major complications (4.2%), 26 in group A (6.2%) and 5 in group B (1.6%) (P=.002). The implementation of the new protocol was an independent predictor of the absence of complications (odds ratio=0.406; 95% confidence interval, 0.214-0.769; P<.006).

Conclusions

Systematic application of an anticoagulation and conscious sedation protocol is associated with improved results and fewer complications of atrial fibrillation ablation. Factors not evaluated in the present study, such as operator experience and ongoing improvements in atrial fibrillation ablation technology, could have influenced these findings.Full English text available from:www.revespcardiol.org     

Age-of-onset of menopause is associated with enhanced painful and non-painful sensitivity in fibromyalgia

Fibromyalgia (FM) is a chronic pain condition characterized by high prevalence in women. In particular, estrogen deficit has been considered as a potentially promoting factor of FM symptoms. This study was aimed to examine the relationship between age-of-onset of menopause and pain sensitivity in FM. For this purpose, pain sensitivity was assessed in 74 FM and 32 pain-free control women. All participants were postmenopausal and underwent a detailed semi-structured clinical interview, including data about menopause transition, previous history of hysterectomy or ovariectomy, and menses time. Participants were divided into two groups depending on age-of-onset of menopause: early menopause [≤49 years] vs. late menopause [>49 years]. Pain and non-pain thresholds were assessed by using cold, heat, mechanical, and electrical stimulation. FM women showed higher overall pain sensitivity as compared with healthy subjects. FM women with early age-of-onset of menopause displayed greater pain and non-pain sensitivity than FM women with late age-of-onset of menopause, whereas no differences were observed in healthy women due to age-of-onset of menopause. These results suggest that an early transition to menopause (shortening the time of exposure to estrogens) may influence pain hypersensitivity and could be related to aggravation of FM symptoms.