Multiple calcium channels regulate neurotransmitter release from vagus nerve terminals in the cat bronchiole

Abstract

1 Twitch-like contractions and non-adrenergic non-cholinergic (NANC) relaxations evoked by electrical ®eld stimulation (EFS) of the cat bronchiole were used to examine the voltage-activated calcium channels involved in excitatory and inhibitory neurotransmission in the cat bronchiole. 2 Nifedipine (50 mM), the L-type calcium channel antagonist, did not aect the twitch-like contraction and NANC relaxations. However, low concentrations of the N-type calcium channel blocker o-conotoxin GVIA (o-CgTX GVIA) (0.1 mM) irreversibly abolished twitch-like contractions evoked by trains of EFS 410 stimuli at 20 Hz. 3 After the prolonged treatment with 0.1 mM o-CgTX GVIA, EFS evoked initial fast and later slow NANC relaxations in the presence of 5-HT (10 mM), atropine and guanethidine (1 mM each). However increased concentration of o-CgTX GVIA (1 mM) completely suppressed the slow NANC relaxation without aecting the initial fast component. 4 o-agatoxin IVA (100 nM), the P-and Q-type calcium channel inhibitor, and nimodipine (10 mM), the L-and T-type calcium channel blocker, did not aect the amplitude of the initial fast NANC relaxation in the absence or presence of o-CgTX GVIA (1 mM). 5 The contraction or relaxation induced by exogenous acetylcholine (ACh) (0.5 mM) or the nitric oxide donor, s-nitroso-N-acetyl penicillamine (SNAP) (1 mM) were not aected by o-CgTX GVIA (1 mM). 6 Taken together, these results suggest that generation of twitch-like contraction and later slow NANC relaxation are regulated by N-type calcium channels, whereas generation of the initial fast NANC relaxation possibly involves R-type calcium channel.

Presynaptic ‘Cav2.3‐containing’ E‐type Ca2+ channels share dual roles during neurotransmitter release

“…A similar mechanism of regulation may be present in vagal nerve terminals in the cat bronchiole, where late slow nonadrenergic and noncholinergic relaxation is regulated by N‐type calcium channels, whereas initial fast nonadrenergic and noncholinergic relaxation depends on R‐type (probably E‐type) calcium channels (Fujisawa et al ., 1999).…”

Prejunctional modulation of non‐adrenergic non‐cholinergic (NANC) inhibitory responses in the isolated guinea‐pig gastric fundus

“…The inability of the ω ‐agatoxin TK 20 to modify the inhibitory response rules out the involvement of voltage‐activated P/Q‐type Ca 2+ ‐channels. Conversely, the inhibitory effect of ω ‐CTX, a specific N‐type Ca 2+ channel blocker 20–22 reveals the participation of such voltage‐activated channel in NANC neurotransmission. On the other hand, the partial inhibitory effect of ω ‐CTX implies that other mechanisms may be involved in the activation of NANC nerve terminals.…”

Effects of selenoprotein P on the contraction and relaxation of the airway smooth muscle

“…Since we have demonstrated that at least two substances, NO or NO-containing compounds for the fast relaxation and VIP or VIPlike peptide for slow relaxation are involved in the NANC relaxations (Matsuzaki et al 1980;Palmer et al 1986;Hakoda et al 1991;Takahashi et al 1995;Tanaka et al 1996), and that N-type calcium-channel blocker ω-CgTX GVIA (1 µM) selectively and completely suppresses the second slow NANC relaxation without affecting the initial fast component. The initial fast component is also insensitive to P-and Q-type calcium channel blocker ω-agatoxin and the L-and T-type calcium channel blocker nimodipine, thereby indicating that the initial fast NANC relaxation is due to the activation of R-type calcium channel in the pre-synaptic nerve terminal (Fujisawa et al 1999). As shown in Figure 2D, ω-CgTX GVIA abolished the second slow NANC relaxation, and the amplitude of fast NANC relaxation which was sensitive to L-NAME (10 µM) or TTX (0.1 µM), was not affected at all by SeP (3 µM) ( Fig.…”