TRP Ion Channels And FKBP1B Play Crital Roles In Bat Hibernation

Bats,the order Chiroptera,are unique mammals capable of self-powered flight.More than 1,200 species of them have been recognized and most bats can hibernate against cold winter and food shortage.Hibernation is a time period composed of a repeated torpor and arousal episodes.During torpor,the body temperature,heart rate,and metabolic rate of hibernating bats are dropped to an extremely low level,however these physiological parameters recover quickly during arousal.Related genomics and proteomics studies have shown that most of the genes and protein expression are significantly downregulated during torpor.During hibernation,body temperature of hibernators has undergone violent fluctuations,but there was not pathological damage.The molecular mechanism of regulating body temperature is unclear.Temperature-sensitive transient receptor potential ion channels,i.e.,thermo-TRP ion channels,play pivotal roles in thermal sensation.We compared gene expressions of ten thermo-TRP ion channels,including TRPV1,TRPV2,TRPV3,TRPV4,TRPM2,TRPM4,TRPM5,TRPM8,TRPC5 and TRPA1 in the brain between torpid and arousal Myotis ricketti using quantitative RT-PCR.Results showed that the mRNA level of warm-sensitive TRPV1,TRPV2,TRPV3 and TRPV4 and cold sensitive TRPA1 was significantly higher in torpid than in arousal bats.In contrast,the cold sensitive TRPM8 and TRPC5 and thermo-sensitive TRPM2,TRPM4 and TRPM5 had lower expression in torpid bats.We also compared the protein amount of six thermo-TRP ion channels between different hibernation states of the bat using Western blotting(WB).The data of WB generally agree with the results from quantitative RT-PCR.Moreover,a lower UCP1 level found in the brain of torpid bats further supports that thermo-TRP ion channels remian their function during bat hibernation.Taken together,these data suggest that torpid M.ricketti miantian high sensitivity to rising temperature.This study provides the first molecular evidence for thermosensing in hibernating mammals.Hibernators maintain their heart function when the ambient temperature is as low as 10?-15?.Heart failure can be caused by the reduction in calcium levels in sarcoplasmic reticulum(SR).The FKBP1B is the key protein subunit that regulates the concentration of.calcium by adjusting the open-and closed-state of RyR2 ion channel located in the sarcoplasmic reticulum.In order to study the role of FKBP1B in the heart of hibernating bats,we analyzed FKBP1B sequences from a total of 25 mammalian species(including 12 bat species).Results of molecular evolutionary analysis demonstrated that FKBP1B gene was conserved across the bat species.We also compared mRNA and protein levels of FKBP1B in the hearts of two distantly related hibernating bats Myotis ricketti and Rhinolophus ferrumequinum at torpid,2 hours after arousal,24 hours after arousal and active state.Results showed that the mRNA and protein level of FKBP1B was significantly higher in both species of bats during torpor.In addition,the transcription factors(TFs)that may be involved in the regulation of FKBP1B expression were bioinformatically analyzed in 48 hibernating and 15 non-hibernating mammalian species.We found that TFs,such as the transcriptional factor YY1 may play an important role in the regulation of FKBP1B expression during bat hibernation.Our study brings new insights in heart regulation of torpid mammals.In addition,the transcription factors(TFs)that may be involved in the regulation of FKBP1B expression were bioinformatically analyzed in 48 hibernating and 15 non-hibernating mammalian species.We found that TFs,such as the transcriptional factor YY1 may play an important role in the regulation of FKBP1B expression during bat hibernation.This study reveals that hibernating bats maintain the stability of cardiac function by upregulating the expression of FKBP1B.Our study brings new insights in heart regulation of hibernating mammals.