Spermine attenuates carotid body glomus cell oxygen sensing by inhibiting L-type Ca²(+) channels.
An increase in intracellular Ca²(+) is crucial to O₂ sensing by the carotid body. Polyamines have been reported to modulate both the extracellular Ca²(+)-sensing receptor (CaR) and voltage-gated Ca²(+) channels in a number of cell types. Using RT-PCR and immunohistochemistry, the predominant voltage-gated Ca²(+) channels expressed in the adult rat carotid body were L (Ca(V)1.2) and N (Ca(V)2.2)-type. CaR mRNA could not be amplified from carotid bodies, but the protein was expressed in the nerve endings. Spermine inhibited the hypoxia-evoked catecholamine release from isolated carotid bodies and attenuated the depolarization- and hypoxia-evoked Ca²(+) influx into isolated glomus cells. In agreement with data from carotid body, recombinant Ca(V)1.2 was also inhibited by spermine. In contrast, the positive allosteric modulator of CaR, R-568, was without effect on hypoxia-induced catecholamine release from carotid bodies and depolarization-evoked Ca²(+) influx into glomus cells. These data show that spermine exerts a negative influence on carotid body O₂ sensing by inhibiting L-type Ca²(+) channels.
Cayzac
S H
SH
Division of Pathophysiology and Repair, School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3AX, UK.
Rocher
A
A
Obeso
A
A
Gonzalez
C
C
Riccardi
D
D
Kemp
P J
PJ
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism*; D020864:Calcium Channels, N-Type / Q000235:genetics / Q000378:metabolism; D002344:Carotid Body / Q000166:cytology* / Q000187:drug effects; D002395:Catecholamines / Q000378:metabolism; D002628:Chemoreceptor Cells / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D010100:Oxygen / Q000378:metabolism*; D018408:Patch-Clamp Techniques / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044169:Receptors, Calcium-Sensing / Q000235:genetics / Q000378:metabolism*; D013096:Spermine / Q000494:pharmacology*; D014162:Transfection / Q000379:methods
C503279:Cacna1b protein, rat; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D002395:Catecholamines; C419385:L-type calcium channel alpha(1C); D012333:RNA, Messenger; D044169:Receptors, Calcium-Sensing; D013096:Spermine; D010100:Oxygen; D002118:Calcium