Mitochondrial Ca2+ uniporter blockers influence activation-induced CBF response in the rat somatosensory cortex.
Effects of mitochondrial calcium signaling blockade on neural activation-induced CBF response were studied in urethane-anesthetized rats. Ruthenium red (RuR), a nonspecific inhibitor of the mitochondrial calcium uniporter (MCU), and Ru360, a highly specific inhibitor of the MCU, were delivered intravenously (i.v.) or intracerebroventricularly (i.c.v.). Baseline cerebral blood flow (CBF) and cerebral hyperemic response to whisker stimulation were measured through a thinned skull over the somatosensory cortex using laser Doppler imaging (LDI). Ruthenium red or Ru360 did not alter the baseline CBF at all doses used. However, the hyperemic response, defined as the activation area and amplitude of CBF increase in response to mechanical whisker stimulation, was significantly reduced in the presence of either RuR or Ru360 delivered i.c.v. The hyperemic response reduced significantly with a dose of 14.5 nmol RuR (i.c.v.), showing a further decrease with 29 nmol RuR (i.c.v.). A comparable decrease in the hyperemic response was observed during treatment with a relatively lower dose of 4.5 and 9 nmol Ru360 (i.c.v.). Delivered intravenously, Ru360 significantly diminished the cerebral hyperemic response at doses greater than 80 microg/kg i.v., up to a dose of 320 microg/kg i.v. However, RuR (i.v.) had an opposite effect with an enhancement in the cerebral hyperemic response at all doses studied. Ruthenium red or Ru360 had no significant effect on the cerebral reactivity to hypercapnia, indicating that altered cerebral hyperemic response to whisker stimulation was predominantly neural. We conclude that mitochondrial calcium signaling through the MCU mediates neural activation-induced CBF response in vivo.
Kannurpatti
Sridhar S
SS
Department of Radiology, UMDNJ-New Jersey Medical School, Newark, New Jersey 07103, USA. kannursr@umdnj.edu
Biswal
Bharat B
BB
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D019069:Cell Respiration / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D007091:Image Processing, Computer-Assisted; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D017078:Laser-Doppler Flowmetry; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017975:Ruthenium Compounds / Q000008:administration & dosage; D012430:Ruthenium Red / Q000008:administration & dosage; D013003:Somatosensory Cortex / Q000098:blood supply* / Q000378:metabolism*; D014738:Vibrissae / Q000294:innervation
D015220:Calcium Channels; C112020:Ru 360; D017975:Ruthenium Compounds; C034703:mitochondrial calcium uniporter; D012430:Ruthenium Red