Histamine modulates high-voltage-activated calcium channels in neurons dissociated from the rat tuberomammillary nucleus.
The effects of histamine on high-voltage-activated Ca2+ channels in the histaminergic neurons acutely dissociated from the rat tuberomammillary nucleus were investigated in the nystatin-perforated patch recording mode under voltage-clamp conditions. Histamine suppressed the high-voltage-activated Ca2+ channel currents in neurons which were positive for histidine decarboxylase with immunocytochemistry. The half-maximum inhibitory concentration and maximum inhibition were 2.6 x 10(-7) M and 16.6+/-1.90%, respectively. An H3 receptor agonist, R(-)-alpha-methylhistamine, mimicked the response to histamine, and thioperamide, an H3 receptor antagonist, inhibited the response to histamine. On the other hand, neither 2-methylhistamine, an H1 receptor agonist, nor dimaprit, an H2 receptor agonist, had a significant effect on the Ca2+ channel currents. Pretreatment with pertussis toxin blocked the inhibitory effect of histamine on Ca2+ channels, suggesting the involvement of Gi/Go proteins in the action of histamine. Omega-conotoxin-GVIA, omega-agatoxin-IVA, nicardipine, and omega-conotoxin-MVIIC blocked the high-voltage-activated Ca2+ channel currents by 15.6, 4.3, 27.1, and 31.2% of the total current, respectively, suggesting the existence of N-, P-, L-, and Q-type Ca2+ channels. A current that was insensitive to these blockers was also found. This residual current, "R-type", was completely suppressed by the addition of 200 microM Cd2+. Histamine significantly inhibited both the N- and P-type current components among these five types of Ca2+ channel currents. We concluded that histamine suppresses the N- and P-type Ca2+ channels in histaminergic neurons through an H3 receptor which is linked to a pertussis toxin-sensitive G-protein.
Department of Internal Medicine I, Faculty of Medicine, Oita Medical University, Japan.
Y
Y
Takeshita
T
T
Watanabe
T
T
Sakata
M
M
Munakata
H
H
Ishibashi
N
N
Akaike
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000145:classification / Q000187:drug effects* / Q000378:metabolism; D020864:Calcium Channels, N-Type; D003864:Depression, Chemical; D017259:Dimaprit / Q000031:analogs & derivatives / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology*; D017442:Histamine Agonists / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects*; D008326:Mammillary Bodies / Q000166:cytology*; D008761:Methylhistamines / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009529:Nicardipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D037342:Pertussis Toxin; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018100:Receptors, Histamine H3 / Q000187:drug effects; D013111:Spider Venoms / Q000494:pharmacology; D014371:Tuber Cinereum / Q000166:cytology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA; D020960:omega-Conotoxins
D002118:Calcium; D015220:Calcium Channels; D020864:Calcium Channels, N-Type; D017259:Dimaprit; D006632:Histamine; D017442:Histamine Agonists; D006633:Histamine Antagonists; D008761:Methylhistamines; D009419:Nerve Tissue Proteins; D009529:Nicardipine; D010455:Peptides; D037342:Pertussis Toxin; D010880:Piperidines; D018100:Receptors, Histamine H3; D013111:Spider Venoms; D010566:Virulence Factors, Bordetella; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA; D020960:omega-Conotoxins; C053157:omega-conotoxin receptor; C075851:omega-conotoxin-MVIIC; C025838:nordimaprit; C069357:alpha-methylhistamine; C026259:2-methylhistamine; C052075:thioperamide