Involvement of different calcium channels in the depolarization-evoked release of noradrenaline from sympathetic neurones in rabbit carotid artery.

The calcium channels coupled to noradrenaline release from sympathetic neurones in the rabbit isolated carotid artery were examined. Rings of carotid artery were preloaded with (-)-[(3)H]noradrenaline and the fractional (3)H overflow evoked by electrical-field stimulation was determined by liquid scintillation spectrometry. The N-type Ca(2+) channel blocking agent omega-conotoxin GVIA (3x10(-9)-6x10(-8) M) reduced the stimulation-evoked (3)H overflow. The maximal inhibition was seen with 3x10(-8) M. The maximal reduction was more marked at a low (2 Hz) stimulation frequency than at a high one (30 Hz). Mibefradil (10(-6) M) irreversibly reduced the (3)H overflow evoked by field stimulation (2 Hz). At 30 Hz, the reduction was more marked than at 2 Hz. Mibefradil (3x10(-6)-10(-5) M) enhanced the passive (3)H outflow. The reduction of the stimulation (30 Hz)-evoked (3)H overflow seen with omega-conotoxin GVIA (3x10(-8) M) was enhanced by mibefradil (10(-6) M) and unaffected by nimodipine (10(-5) M) and omega-agatoxin IVA (10(-8) M). We conclude that the stimulation-evoked release of noradrenaline from sympathetic neurones in rabbit carotid artery at a low frequency (2 Hz) is mediated mainly by the N-type calcium channels. At a high frequency (30 Hz), T-type Ca(2+) channels are also involved.