Abstract
Damaraland and naked mole rat are eusocial mammals that live in crowded burrows in which CO2 is elevated. These species are thought to be highly tolerant of CO2 but their behavioural responses to hypercapnia are poorly understood. We hypothesized that Damaraland and naked mole rats would exhibit blunted behavioural responses to hypercapnia and predicted that their activity levels would be unaffected at low to moderate (2–5%) CO2 but increased at > 7% CO2. To test this, we exposed Damaraland and naked mole rats to stepwise increases in environmental CO2 (0–10%) and measured activity, exploratory behaviour, and body temperature. Surprisingly, we found that both species exhibited no differences in movement velocity, distance travelled, zone transitions (exploration), or body temperature at any level of environmental hypercapnia. Conversely, when carbonic anhydrase was inhibited with acetazolamide (50 mg kg−1 intraperitonially, to increase whole-animal acidosis), exploration was significantly elevated relative to hypercapnic controls in both species at all levels of inhaled CO2, and naked mole rat body temperature decreased in > 7% CO2. We conclude that both species are largely non-responsive to environmental CO2, and that this tolerance may be dependent on bicarbonate buffering at the level of the kidney or within the blood.
Similar content being viewed by others
References
Arieli R (1979) The atmospheric environment of the fossorial mole rat (Spalax ehrenbergi): effects of season, soil texture, rain, temperature and activity. Comp Biochem Physiol 63A:569–575
Arieli R, Ar A (1979) Ventilation of a fossorial mammal (Spalax ehrenbergi) in hypoxic and hypercapnic conditions. J Appl Physiol Respir Environ Exerc Physiol 47(5):1011–1017
Bigatello LM, Patroniti N, Sangalli F (2001) Permissive hypercapnia. Curr Opin Crit Care 7(1):34–40
Boggs DF, Kilgore DL, Birchard GF (1984) Respiratory physiology of burrowing mammals and birds. Comp Biochem Physiol 77:1–7
Boyles JG, Verburgt L, Mckechnie AE, Bennett NC (2012) Heterothermy in two mole-rat species subjected to interacting thermoregulatory challenges. J Exp Zool A 317a(2):73–82. https://doi.org/10.1002/jez.723
Brand A, Smith ES, Lewin GR, Park TJ (2010) Functional neurokinin and NMDA receptor activity in an animal naturally lacking substance P: the naked mole-rat. PLoS One 5(12):e15162. https://doi.org/10.1371/journal.pone.0015162
Buffenstein R, Yahav S (1991) Is the naked mole-rat Hererocephalus glaber an endothermic yet poikilothermic mammal? J Therm Biol 16(4):227–232
Chung D, Dzal YA, Seow A, Milsom WK, Pamenter ME (2016) Naked mole rats exhibit metabolic but not ventilatory plasticity following chronic sustained hypoxia. Proc Biol Sci. https://doi.org/10.1098/rspb.2016.0216
Clapp JR, Watson JF, Berliner RW (1963) Effect of carbonic anhydrase inhibition on proximal tubular bicarbonate reabsorption. Am J Physiol 205:693–696. https://doi.org/10.1152/ajplegacy.1963.205.4.693
Cogan MG, Maddox DA, Warnock DG, Lin ET, Rector FC Jr (1979) Effect of acetazolamide on bicarbonate reabsorption in the proximal tubule of the rat. Am J Physiol 237(6):F447–F454. https://doi.org/10.1152/ajprenal.1979.237.6.F447
Daly TJM, Williams LA, Buffenstein R (1997) Catecholaminergic innervation of interscapular brown adipose tissue in the naked mole-rat (Heterocephalus glaber). J Anat 190(3):321–326
Darden TR (1972) Respiratory adaptations of a fossorial mammal, the pocket gopher (Thomomys bottae). J Comp Physiol 78:121–137
Dresler T, Guhn A, Tupak SV, Ehlis AC, Herrmann MJ, Fallgatter AJ, Deckert J, Domschke K (2013) Revise the revised? New dimensions of the neuroanatomical hypothesis of panic disorder. J Neural Transm (Vienna) 120(1):3–29. https://doi.org/10.1007/s00702-012-0811-1
Dzal YA, Jenkin SEM, Lague SL, Reichert MN, York JM, Pamenter ME (2015) Oxygen in demand: how oxygen has shaped vertebrate physiology. Comp Biochem Physiol A 186:4–26. https://doi.org/10.1016/j.cbpa.2014.10.029
Elam M, Yao T, Thoren P, Svensson TH (1981) Hypercapnia and hypoxia—chemoreceptor-mediated control of locus coeruleus neurons and splanchnic, sympathetic-nerves. Brain Res 222(2):373–381. https://doi.org/10.1016/0006-8993(81)91040-4
Garcia-Marin JJ, Dumont M, Corbic M, de Couet G, Erlinger S (1985) Effect of acid–base balance and acetazolamide on ursodeoxycholate-induced biliary bicarbonate secretion. Am J Physiol 248(1 Pt 1):G20–G27. https://doi.org/10.1152/ajpgi.1985.248.1.G20
Gorman JM, Liebowitz MR, Fyer AJ, Stein J (1989) A neuroanatomical hypothesis for panic disorder. Am J Psychiatry 146(2):148–161. https://doi.org/10.1176/ajp.146.2.148
Granjeiro EM, da Silva GS, Giusti H, Oliveira JA, Glass ML, Garcia-Cairasco N (2016) Behavioral, ventilatory and thermoregulatory responses to hypercapnia and hypoxia in the Wistar audiogenic rat (WAR) strain. PLoS One 11(5):e0154141. https://doi.org/10.1371/journal.pone.0154141
Hanson CW 3rd, Marshall BE, Frasch HF, Marshall C (1996) Causes of hypercarbia with oxygen therapy in patients with chronic obstructive pulmonary disease. Crit Care Med 24(1):23–28
Heller I, Halevy J, Cohen S, Theodor E (1985) Significant metabolic acidosis induced by acetazolamide. Not a rare complication. Arch Intern Med 145(10):1815–1817
Holtze S, Braude S, Lemma A, Koch R, Morhart M, Szafranski K, Platzer M, Alemayehu A, Goeritz F, Hildebrandt TB (2018) The microenvironment of naked mole-rat burrows in East Africa. Afr J Ecol 56(2):279–289. https://doi.org/10.1111/aje/12448
Houlahan CR, Kirby AM, Dzal YA, Fairman GD, Pamenter ME (2018) Divergent behavioural responses to acute hypoxia between individuals and groups of naked mole rats. Comp Biochem Physiol B. https://doi.org/10.1016/j.cbpb.2018.01.004
Ilacqua AN, Kirby AM, Pamenter ME (2017) Behavioural responses of naked mole rats to acute hypoxia and anoxia. Biol Lett. https://doi.org/10.1098/rsbl.2017.0545
Jacobson HR (1981) Effects of CO2 and acetazolamide on bicarbonate and fluid transport in rabbit proximal tubules. Am J Physiol 240(1):F54–F62. https://doi.org/10.1152/ajprenal.1981.240.1.F54
Johnson PL, Fitz SD, Hollis JH, Moratalla R, Lightman SL, Shekhar A, Lowry CA (2011) Induction of c-Fos in ‘panic/defence’-related brain circuits following brief hypercarbic gas exposure. J Psychopharmacol 25(1):26–36. https://doi.org/10.1177/0269881109353464
Kirby AM, Fairman G, Pamenter ME (2018) Atypical behavioural, metabolic, and thermoregulatory responses to hypoxia in the naked mole rat (Heterocephalus glaber). J Zool 305(2):106–115. https://doi.org/10.1111/jzo.12542
Klein DF (1993) False suffocation alarms, spontaneous panics, and related conditions. An integrative hypothesis. Arch Gen Psychiatry 50(4):306–317
Kuhnen G (1986) O2 and CO2 concentrations in burrows of euthermic and hibernating golden hamsters. Comp Biochem Physiol A 84(3):517–522
Lavinka PC, Park TJ (2012) Blunted behavioral and C fos responses to acidic fumes in the african naked mole-rat. PLoS One 7(9):e45060. https://doi.org/10.1371/journal.pone.0045060 (PONE-D-12-04774 [pii])
Madsen PO (1954) The effect of the carbonic anhydrase inhibitor, diamox, on urine electrolytes in normal and adrenalectomized dogs, and its possible relationship to serum bicarbonate. Acta Physiol Scand 31(1):28–35. https://doi.org/10.1111/j.1748-1716.1954.tb01112.x
Marotta SF, Sithichoke N, Garcy AM, Yu M (1976) Adrenocortical responses of rats to acute hypoxic and hypercapnic stresses after treatment with aminergic agents. Neuroendocrinology 20(2):182–192. https://doi.org/10.1159/000122482
Mcnab BK (1966) The metabolism of fossorial rodents: a study of convergence. Ecology 47:712–733
Oosthuizen MK, Cooper HM, Bennett NC (2003) Circadian rhythms of locomotor activity in solitary and social species of African mole-rats (family: Bathyergidae). J Biol Rhythm 18(6):481–490. https://doi.org/10.1177/0748730403259109
Pamenter ME, Dzal YA, Milsom WK (2015) Adenosine receptors mediate the hypoxic ventilatory response but not the hypoxic metabolic response in the naked mole rat during acute hypoxia. Proc Biol Sci 282(1800):20141722. https://doi.org/10.1098/rspb.2014.1722
Pamenter ME, Lau GY, Richards JG, Milsom WK (2018) Naked mole rat brain mitochondria electron transport system flux and H(+) leak are reduced during acute hypoxia. J Exp Biol. https://doi.org/10.1242/jeb.171397
Papp LA, Martinez JM, Klein DF, Coplan JD, Norman RG, Cole R, de Jesus MJ, Ross D, Goetz R, Gorman JM (1997) Respiratory psychophysiology of panic disorder: three respiratory challenges in 98 subjects. Am J Psychiatry 154(11):1557–1565. https://doi.org/10.1176/ajp.154.11.1557
Park TJ, Lu Y, Juttner R, Smith ES, Hu J, Brand A, Wetzel C, Milenkovic N, Erdmann B, Heppenstall PA, Laurito CE, Wilson SP, Lewin GR (2008) Selective inflammatory pain insensitivity in the African naked mole-rat (Heterocephalus glaber). PLoS Biol 6(1):e13. https://doi.org/10.1371/journal.pbio.0060013
Park TJ, Reznick J, Peterson BL, Blass G, Omerbasic D, Bennett NC, Kuich P, Zasada C, Browe BM, Hamann W, Applegate DT, Radke MH, Kosten T, Lutermann H, Gavaghan V, Eigenbrod O, Begay V, Amoroso VG, Govind V, Minshall RD, Smith ESJ, Larson J, Gotthardt M, Kempa S, Lewin GR (2017) Fructose-driven glycolysis supports anoxia resistance in the naked mole-rat. Science 356(6335):307–311. https://doi.org/10.1126/science.aab3896
Riccio AP, Goldman BD (2000a) Circadian rhythms of body temperature and metabolic rate in naked mole-rats. Physiol Behav 71(1–2):15–22
Riccio AP, Goldman BD (2000b) Circadian rhythms of locomotor activity in naked mole-rats (Heterocephalus glaber). Physiol Behav 71(1–2):1–13
Roper TJ, Bennett NC, Conradt L, Molteno AJ (2001) Environmental conditions in burrows of two species of African mole-rat, Georhychus capensis and Cryptomys damarensis. J Zool 254:101–107. https://doi.org/10.1017/S0952836901000590
Schlenker E, Shi Y, Johnson C, Wipf J (2006) Acetazolamide affects breathing differently in ICR and C57 mice. Respir Physiol Neurobiol 152(2):119–127. https://doi.org/10.1016/j.resp.2005.07.006
Shams I, Avivi A, Nevo E (2005) Oxygen and carbon dioxide fluctuations in burrows of subterranean blind mole rats indicate tolerance to hypoxic-hypercapnic stresses. Comp Biochem Physiol A 142(3):376–382. https://doi.org/10.1016/j.cbpa.2005.09.003
Sharabi K, Lecuona E, Helenius IT, Beitel GJ, Sznajder JI, Gruenbaum Y (2009) Sensing, physiological effects and molecular response to elevated CO2 levels in eukaryotes. J Cell Mol Med 13(11–12):4304–4318. https://doi.org/10.1111/j.1582-4934.2009.00952.x
Somers VK, Mark AL, Zavala DC, Abboud FM (1989) Contrasting effects of hypoxia and hypercapnia on ventilation and sympathetic activity in humans. J Appl Physiol (1985) 67(5):2101–2106. https://doi.org/10.1152/jappl.1989.67.5.2101
Streicher S, Boyles JG, Oosthuizen MK, Bennett NC (2011) Body temperature patterns and rhythmicity in free-ranging subterranean Damaraland mole-rats, Fukomys damarensis. Plos One. https://doi.org/10.1371/journal.pone.0026346 (ARTN e26346)
Walker BR (1987) Cardiovascular effect of V-1 vasopressinergic blockade during acute hypercapnia in conscious rats. Am J Physiol 252(1):R127–R133
Williams DD, Rausch RL (1973) Seasonal carbon-dioxide and oxygen concentrations in dens of hibernating mammals (Sciuridae). Comp Biochem Physiol 44(4a):1227. https://doi.org/10.1016/0300-9629(73)90261-2
Yahav S, Buffenstein R (1991) Huddling behavior facilitates homeothermy in the naked mole rat Heterocephalus-glaber. Physiol Zool 64(3):871–884
Yamauchi W, Dostal J, Strohl K (2007) Dose effect of acetazolamide on post-hypoxic unstable breathing in the c57BL/6J mouse. Sleep 30:A164–A164
Yunoki T, Horiuchi M, Yano T (1999) Kinetics of excess CO2 output during and after intensive exercise. Jpn J Physiol 49(2):139–144
Acknowledgements
The authors would like to thank the uOttawa animal care and veterinary services staff for their tireless support and care of our experimental animals. This work was supported by a Natural Sciences and Engineering Research Council of Canada Discovery Grant and a Canada Research Chair (Tier II) to MEP. Animal protocols complied with requirements of the Canadian Council on Animal Care and were approved by the University of Ottawa Animal Care Committee.
Author information
Authors and Affiliations
Contributions
MEP conceived of the project and designed the study. TB and SE performed the experiments and analyzed the data. MEP wrote the manuscript and all authors contributed to editing the manuscript.
Corresponding author
Rights and permissions
About this article
Cite this article
Branigan, T., Elkhalifa, S. & Pamenter, M.E. Behavioural responses to environmental hypercapnia in two eusocial species of African mole rats. J Comp Physiol A 204, 811–819 (2018). https://doi.org/10.1007/s00359-018-1283-z
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00359-018-1283-z