Novel Roles for Kv7 Channels in Shaping Histamine-Induced Contractions and Bradykinin-Dependent Relaxations in Pig Coronary Arteries

Voltage-gated K_v7 channels are inhibited by agonists of G_q-protein-coupled receptors, such as histamine. Recent works have provided evidence that inhibition of vascular K_v7 channels may trigger vessel contractions. In this study, we investigated how K_v7 activity modulates the histamine-induced contractions in “healthy” and metabolic syndrome (MetS) pig right coronary arteries (CAs). We performed isometric tension and immunohistochemical studies with domestic, lean Ossabaw, and MetS Ossabaw pig CAs. We found that neither the K_v7.2/K_v7.4/K_v7.5 activator ML213 nor the general K_v7 inhibitor XE991 altered the tension of CA rings under preload, indicating that vascular K_v7 channels are likely inactive in the preloaded rings. Conversely, ML213 potently dilated histamine-pre-contracted CAs, suggesting that K_v7 channels are activated during histamine applications and yet partially inhibited by histamine. Immunohistochemistry analysis revealed strong K_v7.4 immunostaining in the medial and intimal layers of the CA wall, whereas K_v7.5 immunostaining intensity was strong in the intimal but weak in the medial layers. The medial K_v7 immunostaining was significantly weaker in MetS Ossabaw CAs as compared to lean Ossabaw or domestic CAs. Consistently, histamine-pre-contracted MetS Ossabaw CAs exhibited attenuated ML213-dependent dilations. In domestic pig CAs, where medial K_v7 immunostaining intensity was stronger, histamine-induced contractions spontaneously decayed to ~31% of the peak amplitude within 4 minutes. Oppositely, in Ossabaw CAs, where K_v7 immunostaining intensity was weaker, the histamine-induced contractions were more sustained. XE991 pretreatment significantly slowed the decay rate of histamine-induced contractions in domestic CAs, supporting the hypothesis that increased K_v7 activity correlates with a faster rate of histamine-induced contraction decay. Alternatively, XE991 significantly decreased the amplitude of bradykinin-dependent dilations in pre-contracted CAs. We propose that in CAs, a decreased expression or a loss of function of K_v7 channels may lead to sustained histamine-induced contractions and reduced endothelium-dependent relaxation, both risk factors for coronary spasm.     

Kin Discrimination in a Macropod Marsupial

Differential treatment of kin is ubiquitous in social animals. Parents often behave preferentially towards their dependent offspring. Species in several taxa also bias behaviour towards non-descendent kin. This latter phenomenon has not been demonstrated in marsupials, which are reportedly less social than eutherian mammals. We report the first evidence of non-parental kin-biased behaviour in a macropodid marsupial. Experimental pairing of individuals based on kinship reliably altered the rate of aggression between individuals in pairs of female tammar wallabies ( Macropus eugenii ). This effect is probably attributable to relatedness rather than to familiarity. Marsupial sociality may be substantially more complex than is currently recognized.     

Physiological responses of Sargasso Sea picoplankton to nanomolar nitrate perturbations

A study was conducted in July 1989 at three stations in thenorthern Sargasso Sea, where picoplankton (<1 µm)provided approximately half of the standing crop of chlorophyll.Temporal changes in the position of the nitracline at a singlelocation indicated that the vertical supply of nitrate was notat ‘steady-state’ and phytoplankton distributionstracked the nitracline. Our main experimental objective wasto examine the short-term effects of ecologically significantnitrate perturbations (+20 and +100 nM) on the physiologyof <1 µm communities growing at low (nanomolar)ambient nitrate concentrations. A chemiluminescent nitrate methodwas used to measure the time course (up to 4 h) of nitratedisappearance at in situ irradiance, in parallel with measurementsof photosynthetic ¹⁴CO₂ assimilation. Picoplankton growing at<60 nM nitrate rapidly responded to nanomolar nitratesupplements with luxury consumption and enhanced photosynthesisin proportion to their ambient nitrate environment. Light-saturatedSynechococcus populations from the most nitrate-depleted waters(13 nM) had doubled their cellular rate of photosynthesisafter 4 h, in response to a 20 nM nitrate pulse.     

Structural and functional variability among DQ β alleles of DR2 subtypes

Homozygous lymphoblastoid cell lines representing various Dw subtypes of DR2 were examined for polymorphism at the DQ locus by molecular and cellular techniques. The subtypes studied included Dw2, Dw12, and a group heterogenous by cellular typing that we shall refer to as non-Dw2/non-Dw12. Restriction fragment length polymorphism analysis of cell lines representing these subtypes revealed DQ -specific patterns consistent with cellular typing. Two-dimensional gel electrophoresis of DQ molecules from representative cell lines revealed a structural polymorphism of DQ among the three subtypes. The DQ chain migrated to a position that was unique to each subtype and was consistent among various representative cell lines of each subtype. Nucleotide sequence analysis of cDNA clones of DQ from Dw2, Dw12, and non-Dw2/non-Dw12 lines confirmed that the variability resided at the genetic level. Variability was found in the form of numerous scattered nucleotide substitutions throughout the first domain of these alleles. The DQ gene of the non-Dw2/non-Dw12 cell line AZH was further found to be almost identical with the DQ gene of a DR1 line (Bell et al. 1985b), implicating a common evolutionary origin of these alleles. The only difference between these two sequences was due to an apparent gene conversion event at amino acid 57. T-cell cloning experiments resulted in the derivation of Epstein-Barr virus-specific, DQw1-restricted clones that proliferated against only those cell lines that exhibited the DQ gene common to AZH and the DR1 cell line. Thus, the polymorphism among DQ alleles within DR2 results in subtype-specific restriction.