EFFECTS OF BKCa CHANNELS ON THE REDUCTION OF CYTOSOLIC Ca2+ IN cGMP-INDUCED RELAXATION OF GUINEAPIG TRACHEA

1. In order to examine the mechanisms of cGMP-induced relaxation in airway smooth muscle, the effects of atrial natriuretic peptide (ANP) and 8-brom cGMP on muscle tone were studied by measuring isometric tension, while the effects on cytosolic Ca²⁺ concentrations were studied by measuring the spectra of fura-2 loaded in guinea-pig tracheal strips. 2. Atrial natriuretic peptide and 8-brom cGMP caused a concentration-dependent inhibition of spontaneous tone in the guinea-pig trachea. The relaxant effects of these agents on spontaneous tone were markedly suppressed in the presence of iberiotoxin (IbTX), a selective inhibitor of large-conductance Ca²⁺-activated K⁺ (BKca) channels. Iberiotoxin (30 nmol/L) markedly affected the maximal effect induced by ANP and 8-brom cGMP and augmented EC₇₀ values for ANP and EC₅₀values for 8-brom cGMP approximately 27- and 17-fold, respectively. The inhibitory effects of IbTX on relaxation induced by these agents were diminished in the presence of 1 μmol/L nifedipine, an antagonist of voltage-operated Ca²⁺channels (VOCC). 3. The inhibitory action of ANP and 8-brom cGMP on spontaneous tone was not affected by the presence of 10 μmol/L glibenclamide, an inhibitor of ATP-sensitive K⁺ channels, and 100 nmol/L apamin, an inhibitor of small-conductance Ca²+-activated K⁺ channels. When these agents were applied to tissues precontracted by high (40mmol/L) K⁺, the relaxant effects of these agents markedly diminished. 4. The extracellular Ca²⁺-dependent contraction was inhibited in the presence of 0.3 μmoI/L ANP or 0.1 mmol/L 8-brom cGMP. Concentration—response curves to extracellular Ca²⁺ (0.03—2.4 mmol/L) were markedly diminished by exposure to these agents. The maximal effect induced by extracellular Ca²⁺ was affected by these agents. 5. Atrial natriuretic peptide caused an inhibition of spontaneous tone accompanied by a reduction in the intracellular Ca²⁺ concentration. In the presence of IbTX, the elimination of both muscle tone and cytosolic Ca²⁺ by ANP was suppressed. 6. We conclude that ANP and 8-brom cGMP activate BKca channels and that the inhibition of Ca²⁺ influx through VOCC, mediated by BKca channel activation, may be involved in cGMP-dependent bronchodilation.     

Spectral analysis of intercycle heart fluctuations in the diethyl-ether-anaesthetized or pithed rat treated with l-hyoscyamine

1 Within the context of neural regulation of the activity of sinus node pacemaker cells, the study of heart rate variability, as explored in the frequency domain by spectral analysis, was proposed about 15 years ago as a quantitative tool for the evaluation of short-term autonomic cardiovascular control. It has since been postulated that the two main oscillations observed, one at low and the other at high frequency, may respectively be markers of sympathetic vs. vagal efferent cardiac activity, and that the low- and high-frequency signals may reflect a reciprocal or ‘push–pull’ relationship between sympathetic and parasympathetic control. 2 In our power spectra assessment, ECG R–R intervals were submitted to fast Fourier transformation analysis in order to study the mechanisms underlying the control of heart beats in rats. Data were acquired in conditions of steady arterial blood pressure and cardiac and respiratory activity (spontaneous or artificially stimulated) in diethyl-ether-anaesthetized and pithed rats, as well as in a group of control rats, all in the presence and absence of l-hyoscyamine. 3 With increasing doses of the parasympathetic antagonist, the fractal dimension of the time-series structure remained stable in most cases. The low-frequency spectral component narrowed with increasing drug doses and the high-frequency band underwent either no, or only very slight, changes. 4 In these rodent assays, the low- and high-frequency signals cannot be interpreted as a push–pull relationship between sympathetic and parasympathetic control.     

Myelolipoma of the thoracic spine.

We describe a myelolipoma of the thoracic spine in a patient with gradual and progressive myelopathy. MR imaging showed this predominately fatty lesion to be extradural in location.     

Infectivity of African cassava mosaic virus clones to cassava by biolistic inoculation

Summary.  Clones of an African cassava mosaic virus isolate originating from Nigeria (ACMV-NOg) were shown to be infectious to cassava by biolistic inoculation. The production of pseudorecombinants between ACMV-NOg and clones of an ACMV isolate originating from Kenya (ACMV-K) indicated that the lack of infectivity of ACMV-K to cassava was due to defect(s) in the DNA B genomic component; this component encodes two proteins involved in cell-to-cell movement. This is the first demonstration of infectivity of a cloned geminivirus to cassava and conclusively proves that ACMV is the causative agent of cassava mosaic disease. The potential uses of infectious ACMV clones and the means by which to introduce them into cassava are discussed. Received January 18, 1998 Accepted May 27, 1998     

The case of the missing secretary: DHEW's failed efforts to create a Cabinet secretary of health.

In response to professional and political pressures in 1967, an incident occurred at the Department of Health, Education, and Welfare that illustrates the delicacy and complexity of the legislative process. In an effort to bypass interest group influences, the undersecretary of the Department undertook a maneuver that backfired and frustrated an opportunity that might have resulted in the establishment of a Cabinet office of Health. In addition to demonstrating the sensitivity of the legislative process, and the dangers of overconfidence in dealing with the process, the events also offer moral guidance: too stubborn, idealistic convictions of good people, however well intentioned the actions, may serve to defeat the desired ends.