PMID- 24667981
OWN - NLM
STAT- MEDLINE
DCOM- 20150116
LR  - 20211021
IS  - 1573-6903 (Electronic)
IS  - 0364-3190 (Linking)
VI  - 39
IP  - 5
DP  - 2014 May
TI  - Large conductance calcium-activated potassium channels: their expression and 
      modulation of glutamate release from nerve terminals isolated from rat trigeminal 
      caudal nucleus and cerebral cortex.
PG  - 901-10
LID - 10.1007/s11064-014-1287-1 [doi]
AB  - Large conductance, calcium-activated potassium channels [big potassium (BK) 
      channel] consist of a tetramer of pore-forming alpha-subunit and distinct accessory 
      beta-subunits (beta1-4) that modify the channel's properties. In this study, we 
      analyzed the effects of BK channel activators and blockers on glutamate and 
      gamma-aminobutyric acid (GABA) release from synaptosomes isolated from the cerebral 
      cortices or trigeminal caudal nuclei (TCN) of rats. Real-time polymerase chain 
      reaction was used to characterize BK channel alpha and beta(1-4) subunit expression in 
      the cortex and in the trigeminal ganglia (TG), whose neurons project primary 
      terminal afferents into the TCN. Immunocytochemistry was used to localize these 
      subunits on cortical and TCN synaptosomes. The BK channels regulating 
      [(3)H]D-aspartate release from primary afferent nerve terminals projecting into 
      the TCN displayed limited sensitivity to iberiotoxin, whereas those expressed on 
      cortical synaptosomes were highly sensitive to this toxin. BK channels did not 
      appear to be present on GABAergic nerve terminals from the TCN since 
      [(3)H]-gamma-aminobutyric acid release in this model was unaffected by BK channel 
      activators or blockers. Gene expression studies revealed expression levels of the 
      alpha subunit in the TG that were only 31.2 +/- 2.1% of those found in cortical 
      tissues. The beta4 subunit was the accessory subunit expressed most abundantly in 
      both the cortex and TG. Levels of beta1 and beta2 were low in both these areas although 
      beta2 expression in the TG was higher than that found in the cortex. 
      Immunocytochemistry experiments showed that co-localization of alpha and beta4 subunits 
      (the accessory subunit most abundantly expressed in both brain areas) was more 
      common in TCN synaptosomes than in cortical synaptosomes. On the basis of these 
      findings, it is reasonable to hypothesize that BK channels expressed on 
      glutamatergic terminals in the TCN and cortex have distinct pharmacological 
      profiles, which probably reflect different alpha and beta subunit combinations. Channels 
      in the cortex seem to be composed mainly of alpha subunits and to a lesser degree by 
      alpha and beta4 subunits, whereas in the TG the alpha + beta4 combination seems to prevail 
      (although alpha and/or alpha + beta2 channels cannot be excluded). In light of the BK 
      channels' selective control of excitatory transmission and their pharmacological 
      diversity, their effects on primary glutamatergic afferents projecting to TCN 
      represent a potential target for drug therapy of migraines and other types of 
      orofacial pain.
FAU - Samengo, Irene
AU  - Samengo I
AD  - Institute of Pharmacology, School of Medicine, Catholic University of the Sacred 
      Heart, Largo F. Vito 1, 00168, Rome, Italy.
FAU - Curro, Diego
AU  - Curro D
FAU - Barrese, Vincenzo
AU  - Barrese V
FAU - Taglialatela, Maurizio
AU  - Taglialatela M
FAU - Martire, Maria
AU  - Martire M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140326
PL  - United States
TA  - Neurochem Res
JT  - Neurochemical research
JID - 7613461
RN  - 0 (Benzimidazoles)
RN  - 0 (Indoles)
RN  - 0 (Large-Conductance Calcium-Activated Potassium Channels)
RN  - 0 (Peptides)
RN  - 0 (Protein Subunits)
RN  - 153587-01-0 (NS 1619)
RN  - 30KYC7MIAI (Aspartic Acid)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 3T9U9Z96L7 (paxilline)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - 773HER9B6T (iberiotoxin)
SB  - IM
MH  - Animals
MH  - Aspartic Acid/metabolism
MH  - Benzimidazoles/pharmacology
MH  - Cerebral Cortex/*metabolism
MH  - Glutamic Acid/*metabolism
MH  - Indoles/pharmacology
MH  - Large-Conductance Calcium-Activated Potassium Channels/*biosynthesis/drug 
      effects/physiology
MH  - Male
MH  - Peptides/pharmacology
MH  - Protein Subunits/metabolism
MH  - Rats, Wistar
MH  - Synaptosomes/metabolism
MH  - Trigeminal Caudal Nucleus/*metabolism
MH  - gamma-Aminobutyric Acid/metabolism
EDAT- 2014/03/29 06:00
MHDA- 2015/01/17 06:00
CRDT- 2014/03/27 06:00
PHST- 2014/01/20 00:00 [received]
PHST- 2014/03/14 00:00 [accepted]
PHST- 2014/03/11 00:00 [revised]
PHST- 2014/03/27 06:00 [entrez]
PHST- 2014/03/29 06:00 [pubmed]
PHST- 2015/01/17 06:00 [medline]
AID - 10.1007/s11064-014-1287-1 [doi]
PST - ppublish
SO  - Neurochem Res. 2014 May;39(5):901-10. doi: 10.1007/s11064-014-1287-1. Epub 2014 
      Mar 26.