J. A. Neubauer

Nucleotide sequence of a cDNA encoding rat brain carbonic anhydrase II and its deduced amino acid sequence.

A carbonic anhydrase II (CAII)-encoding cDNA clone was isolated from a rat brain lambda gt11 library. The 1459-bp cDNA codes for 260 amino acids with sequence similarity to mouse and human CAII and hybridizes to a single 1.7-kb mRNA.

Characterization of the rat carbonic anhydrase II gene structure: sequence analysis of the 5′ flanking region and 3′ UTR

The rat carbonic anhydrase II gene was characterized and found to be approximately 15.5 kb in length and to contain 7 exons and 6 introns. All intron/exon junction and branch point sequences conform to consensus sequences, and the overall rat CA II genomic structure appears to be conserved upon comparison with mouse, human, and chicken CA II genes. The putative cis-acting elements within the analyzed 1014 bp 5 flanking region include: TATA box, 4 Sp1 binding sites, 2 AP2 sites and putative tissue-specific beta-globin-like repeat elements. A CpG island of approximately 800 bp was identified that begins about 600 bp upstream of exon 1 and extends about 200 bp into intron 1. In the 3 UTR, two polyadenylation signals (AATAAA) are present, the second of which is believed to be utilized. Northern blot analysis reveals that the 1.7 kb rat CA II mRNA is abundantly expressed in adult male brain and kidney, while negligible amounts are detected in heart and liver.

Hypoxia and Brain Blood Flow

the ascent to high to high altitude presents a variety of physiological and psychological obstacles. The most prominent is the decline in ambient O2 tension (Po2); much of this volume is devoted to consideration of the effects of the resultant hypoxemia on respiration and circulation. It seems likely, however, that acute responses and adaptations to hypoxia in the central nervous system also play key roles in determining man’s ability to ascend to high altitudes. Because, at least in the short run, the O2 supply to the brain at a given Po2 of inspired gas depends largely on ventilation and brain perfusion, the brain blood flow response to hypoxia must be crucial in the integrated physiological responses considered in this chapter.

Modulation of Respiration by Brain Hypoxia

The dual nature of hypoxic modulation of central respiratory activity is best appreciated in the sino-aortic deafferented, anesthetized animal during progressive reductions in the arterial oxygen content.1 Figure 1 illustrates these two distinct central respiratory responses to brain hypoxia and their different oxygen thresholds; respiratory depression, which is manifested with even modest reductions in oxygenation, and respiratory excitation (gasping), which occurs only with severe reductions in the arterial oxygen content (to values less than 20%).

The Modulation of Peripheral Chemoreceptor Input by Central Nervous System Hypoxia

Production of progressive isocapnic brain hypoxia by carbon monoxide (CO) inhalation in anesthetized, vagotomized, peripherally chemodenervated cats results in an initial reduction of phrenic neurogram amplitude followed by a secondary decrease in phrenic burst frequency as the level of hypoxia increases (Melton et al., 1988; Melton et a1.,1990; Wasicko et al., 1990). After arterial O2content (CaO2) is reduced by approximately 50%, the phrenic neurogram becomes silent. Severe depression of the phrenic neurogram during hypoxia does not inhibit the respiratory response to CO2, however, suggesting that processing of central chemoreceptor afferent information is unaffected by hypoxia (Van Beek et al., 1984; Melton et al., 1988)

Time-frequency analysis of the phrenic neurogram during eupnea and gasping using continuous wavelet transform

In this study, the time-ecale representations of the phrenic neurogram of five cata were proposed to characterize the phrenic nerve activity during normal respiration ( e u p nea) and hypoxic gasping using the continuous wavelet transform method. We show that useful information from the approximation of the phrenic neurogram can be extracted by decomposing the phrenic neurogram on a wavelet non orthonormal basis of L*(R) .