Calcium channels at the adrenergic neuroeffector junction in the rabbit ear artery

• Neurotransmitter release is dependent on influx of Ca2+ through voltage-operated calcium channels (VOCCs). These channels may be divided into L, N, T and P subtypes. To investigate the subtypes of VOCC involved in transmitter release from adrenergic nerves in the isolated rabbit ear artery, the effects of some subtype selective VOCC antagonists were examined on contractile responses induced by electrical field stimulation (EFS), and exposure to an isosmolar (low Na+, normal Cl- content) or a hyperosmolar (normal Na+, high Cl- content) 60 mM K+ solution. Tetrodotoxin (TTX) and the L channel blocker nimodipine were present in the latter experiments to inhibit sodium-dependent action potential discharge and the direct contractile effect of K+ depolarization on the smooth muscle cells. Prazosin abolished the contractile effect of EFS, indicating that the response was elicited by activation of adrenergic nerves. The EFS-induced contractions were concentration-dependently inhibited by the N channel blocker omega-conotoxin (pIC50 = 9.0) and the proposed L channel blocker T-cadinol (pIC50 = 4.5), while nimodipine and the T channel blocker tetramethrin had no effect. The isosmolar and hyperosmolar K+ solutions induced a prazosin-sensitive contraction, amounting to 46% and 10% of the response to 10(-5) M noradrenaline (NA), respectively. omega-Conotoxin inhibited the contractile response to the hyperosmolar K+ solution, but not that to the isosmolar K+ solution. T-cadinol preferentially inhibited the response to the hyperosmolar K+ solution. Tetramethrin had no effect on contractions induced by either type of K+ solution.(ABSTRACT TRUNCATED AT 250 WORDS)

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

Nyckelord

Animals

Arteries/metabolism

Calcium Channel Blockers/pharmacology

Calcium Channels/drug effects

Ear/blood supply

Electric Stimulation

Female

In Vitro Techniques

Male

Muscle Contraction/drug effects

Muscle, Smooth, Vascular/drug effects

Neuroeffector Junction/drug effects

Nimodipine/pharmacology

Norepinephrine/pharmacology

Peptides/pharmacology

Potassium Chloride/pharmacology

Prazosin/pharmacology

Pyrethrins/pharmacology

Rabbits

Regional Blood Flow/physiology

Sesquiterpenes/pharmacology

Sympathetic Nervous System/drug effects

Tetrodotoxin/pharmacology

omega-Conotoxins

Publikations- och innehållstyp

art (ämneskategori)

ref (ämneskategori)