Calcium channels involved in noradrenaline release from sympathetic neurones in rabbit carotid artery.
Transmitter release from nerve terminals is dependent on the entry of Ca(2+) through neuronal voltage-gated calcium channels. In sympathetic neurones both N- and L-type calcium channels are present. Potassium channel blockade increases Ca(2+) entry into sympathetic neurones. We examined the participation of N- and L-type calcium channels in the stimulation-evoked release of noradrenaline from vascular sympathetic neurones. Rings of rabbit carotid artery were preincubated with [3H]-noradrenaline. Electrical field stimulation was used to evoke 3H overflow. The selective N-type calcium channel blocking agent omega-conotoxin GVIA (single concentrations: 3 x 10(-10)-10(-8) M) caused a slowly developing reduction of the stimulation-evoked 3H overflow. At 3 x 10(-8) M, omega-conotoxin GVIA caused an equilibrium block with a rapid (15 min.) onset. After 2 hr exposure to omega-conotoxin the inhibition was steady (pIC50 (-log M): 9.43; Emax: 91%). The selective L-type calcium blocking agents nifedipine (10(-7)-10(-5) M) and nimodipine (10(-8)-10(-5) M) had no effect on the stimulation-evoked 3H overflow. The calcium channel opener Bay K 8644 (10-6 M) likewise had no effect. The potassium channel blocking agent 4-aminopyridine (10-5-10-3 M) enhanced the stimulation-evoked 3H overflow up to 5 times. 4-Aminopyridine (10(-4) M) did not alter the inhibitory effect of omega-conotoxin GVIA (3 x 10(-8) M). In the presence of 4-aminopyridine (10(-4) M), nifedipine (10(-5) M) and nimodipine (10(-6) M) enhanced the 3H overflow. We conclude that the stimulation-evoked release of noradrenaline from sympathetic neurones in rabbit carotid artery is mediated by N-type calcium channels and that L-type channels are not involved even when potassium channels are blocked by 4-aminopyridine.
Uhrenholt
Torben R
TR
Department of Physiology and Pharmacology, University of Southern Denmark, Odense, Denmark.
Nedergaard
Ove A
OA
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000502:physiology*; D020864:Calcium Channels, N-Type / Q000502:physiology*; D017536:Carotid Artery, Common / Q000187:drug effects* / Q000294:innervation; D004558:Electric Stimulation; D005260:Female; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D009553:Nimodipine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011817:Rabbits; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects*; D013997:Time Factors; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D026902:Potassium Channel Blockers; D009553:Nimodipine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D020866:omega-Conotoxin GVIA; D015761:4-Aminopyridine; D009543:Nifedipine; D002118:Calcium; D009638:Norepinephrine