Terrestrial snails which live under dry and hot conditions need efficient mechanisms of adaptation to counteract the problems of desiccation and over-heating. A profoundly heat tolerant snail species is the Mediterranean Xeropicta derbentina, exhibiting different shell colour morphs ranging from pale white to darkly banded. Considering that dark-pigmented snails are believed to have a disadvantage due to faster heating, we investigated possible differences in the stress markers Hsp70 and lipid peroxideation between four pre-defined colour morphs which were exposed to different temperatures for eight hours. The highest Hsp70 levels were observed in response to 38-40°C. Levels decreased when this temperature was exceeded. Snails of a pre-defined colour category 3 (with a large black band at the umbilicus side of the shell) showed the most prominent Hsp70 response. Lipid peroxideation levels also showed a maximum at 38°C but displayed a second peak at rather high temperatures at which the Hsp70 level already had decreased (45-48°C). Particularly pure white snails (category 1) and the most pigmented ones (category 4) were found to have different levels of lipid peroxidation at 38°C and 45°C compared to the other morphs. A hypothesis involving a combined two-phase defence mechanism, to which both, the Hsp70 protection system and the antioxidant defence system, may contribute, is discussed.
*EM and TC contributed equally to this work.
BACKGROUND AND PURPOSE
5-HT increases force and L-type Ca2+ current (I Ca,L ) and causes arrhythmias through 5-HT 4 receptors in human atrium. In permanent atrial fibrillation (peAF), atrial force responses to 5-HT are blunted, arrhythmias abolished but I Ca,L responses only moderately attenuated. We investigated whether, in peAF, this could be due to an increased function of PDE3 and/or PDE4, using the inhibitors cilostamide (300 nM) and rolipram (1 μM) respectively.
EXPERIMENTAL APPROACHContractile force, arrhythmic contractions and I Ca,L were assessed in right atrial trabeculae and myocytes, obtained from patients with sinus rhythm (SR), paroxysmal atrial fibrillation (pAF) and peAF.
KEY RESULTSMaximum force responses to 5-HT were reduced to 15% in peAF, but not in pAF. Cilostamide, but not rolipram, increased both the blunted force responses to 5-HT in peAF and the inotropic potency of 5-HT fourfold to sevenfold in trabeculae of patients with SR, pAF and peAF. Lusitropic responses to 5-HT were not decreased in peAF. Responses of I Ca,L to 5-HT did not differ and were unaffected by cilostamide or rolipram in myocytes from patients with SR or peAF. Concurrent cilostamide and rolipram increased 5-HT's propensity to elicit arrhythmias in trabeculae from patients with SR, but not with peAF.
CONCLUSIONS AND IMPLICATIONSPDE3, but not PDE4, reduced inotropic responses to 5-HT in peAF, independently of lusitropy and I Ca,L , but PDE3 activity was the same as that in patients with SR and pAF. Atrial remodelling in peAF abolished the facilitation of 5-HT to induce arrhythmias by inhibition of PDE3 plus PDE4.
Abbreviations
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.