Possible role of apamin-sensitive K+ channels in myotonic dystrophy.

Myotonic muscular dystrophy is a genetic disease characterized mainly by muscle atrophy and myotonia, a repetitive electrical activity of muscle. In the present study, the possible role of apamin-sensitive K+ channels in the genesis of myotonia was investigated. Apamin is a peptide from bee venom that specifically blocks small conductance Ca(2+)-activated K+ channels. The injection of a small amount of apamin (20-30 microliters, 10 mumol/L) into the thenar muscle of myotonic dystrophy patients decreased the basal electrical activity during the electromyogram in the 6 patients studied. Myotonic discharges after muscle percussion were more difficult to trigger and of smaller intensity and duration. In 2 controls and in 2 patients with generalized myotonia, as well as in 1 patient with myotonia congenita (where the defect is in chloride channels), apamin had no effect. These results suggest that apamin-sensitive K+ channels participate in the mechanism that generates myotonia in myotonic dystrophy.

[Early abortion: natural failure or lack of a critical spirit?]. / Aborto precoz: error de la naturaleza o falta de espiritu crítico?

The existence of spontaneous, clinically inapparent early abortions seems to be generally acknowledged in the scientific literature. The lack of scientific criticism about the limitations and inconsistencies on the quantitative estimation of these early losses is however striking. This study examines critically the published primary scientific evidence about early spontaneous clinically inapparent abortions. Three main methods are disclosed: 1) Direct inspection of the uterus and fallopian tubes; 2) Theoretical assumptions, and, 3) Estimates of 'biochemical abortions'. Estimates ranging from 7.6% to 56.8% of all pregnancies are obtained by experimental studies. Actual methodological shortcomings and inter-group variability in results provide no scientific ground for a quantitative agreement. The results of this study preclude the utilization of a precise quantitative estimate of early spontaneous clinically inapparent abortions in any rational discussion, unless new experimental evidence could be provided.

Inhibition in carotid body chemoreceptors mediated by D-2 dopaminoceptors: antagonism by benzamides.

Inhibition of chemosensory nerve impulses in the cat is evoked by dopamine (DA) applied to carotid body chemoreceptors. Pharmacological characterization of the dopaminoceptors involved in this action was determined through their blockade with benzamides, selective antagonists of D-2 receptors. Both metoclopramide and sulpiride were effective blockers of DA-induced chemosensory inhibition. Furthermore, both drugs induced an immediate increase in the frequency of carotid nerve chemosensory impulses, suggesting the presence of previous tonic inhibition of chemoreceptor discharges by endogenous DA released from glomus cells.

Cardiovascular responses to hypoxia in the spontaneously breathing cat: reflexes originating from carotid and aortic bodies.

The heart rate (fH) and systemic arterial pressure (Pa) responses to transient anoxemic and cytotoxic hypoxia were studied in 18 pentobarbitone-anesthetized, spontaneously breathing cats, by applying N2 tests and i.v. injections of NaCN. Hyperventilation was accompanied by short-latency increases in Pa and fH; they persisted after bilateral vagotomy, sparing the aortic nerves. Acute section of carotid or aortic nerves in different sequences reduced both fH and Pa responses, the contribution of both pairs of nerves being similar. The recording of carotid chemosensory discharges showed transient stimulus-dependent increases in their frequency, to which the ensuing fH and Pa rises were correlated. After sectioning the four buffer nerves, hypoxia provoked long-lasting hypotension and bradycardia. Tachycardia was also observed in response to hypoxia in 4 out of 6 chloralose-anesthetized spontaneously breathing cats, the other two presenting bradycardia. The direction of these cyanide-induced changes in fH was not modified by bilateral vagotomy. It is concluded that tachycardia and hypertension in response to hypoxia are not vagally-mediated consequences of hyperventilation.

Relative contribution of carotid and aortic bodies to cyanide-induced ventilatory responses in the cat.

The participation of afferences from carotid and aortic bodies to the hyperventilation caused by cytotoxic hypoxia was assessed in pentobarbitone-anesthetized cats. Dose-response curves for the ventilatory effects induced by i.v. injections of NaCN were obtained before and after successive denervations of peripheral chemoreceptors, in different sequences. Bilateral aortic neurotomy (BAN) or unilateral carotid neurotomy (UCN) did not affect significantly the minimal sensitivity to the drug, although maximal reactivity was reduced in some cats. After bilateral carotid neurotomy (BCN), with preservation of aortic nerves, sensitivity was reduced, but hyperventilation was still provoked by large doses of cyanide. BAN + BCN abolished the ventilatory responses to the drug. In cats with BAN + UCN, ventilatory responses had a high degree of correlation with increases of carotid chemosensory discharges in the range between ca 200% of control and the gasping threshold. It is concluded that the aortic bodies of the cat play a significant role in the hyperventilation produced by cytotoxic hypoxia, although it is less marked than that induced through the carotid bodies.