Depolarizing agents induce oscillations in canine bronchial smooth muscle membrane potential: possible mechanisms.
Tetraethylammonium (TEA) 925 mM), 4-aminopyridine (4-AP) (5 mM) and carbachol (3 X 10(-7) M) elicited membrane depolarization (approximately 20 mV) and oscillation (0.5-1.0 Hz; up to 25 mV in amplitude) in canine bronchi (3rd to 5th order). BaCl2 (1 mM) also elicited large depolarizations but not oscillations. The oscillations were antagonized by nitrendipine (NT) (10(-8) M) or atropine (10(-6) M) and were unaffected by phentolamine, propranolol or apamin (all 10(-7) M). TEA- or 4-AP-induced membrane depolarizations were partially reversed by atropine. After replacement of extracellular Ca++ with Sr++, oscillations elicited by carbachol or TEA were considerably slower (although amplitudes were similar to those seen in Ca++). Excitatory junction potentials were not altered by NT, were inhibited by 4-AP or replacement of extracellular Ca++ with Sr++, were potentiated by Ba++ and were variably affected by TEA. Contractile responses to acetylcholine were supported by Ca++ or Sr++ (with reduced efficacy), and only the latter were sensitive to NT. Our data suggest that, in canine bronchi (3rd to 5th order), 1) there are K+ channels and Ca++ channels (not L-type) on the cholinergic nerve endings, which modulate neurotransmitter release, 2) there are voltage-dependent K+ channels on the smooth muscle, which regulate membrane potential and suppress excitatory activity, and 3) membrane depolarization leads to alternating opening and closing of voltage-dependent (L-type) Ca++ channels on the smooth muscle, producing oscillations in membrane potential.(ABSTRACT TRUNCATED AT 250 WORDS)
Janssen
L J
LJ
Department of Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
Daniel
E E
EE
D000818:Animals; D001980:Bronchi / Q000187:drug effects*; D015220:Calcium Channels / Q000187:drug effects; D004285:Dogs; D004558:Electric Stimulation; D008564:Membrane Potentials / Q000187:drug effects*; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D015220:Calcium Channels; D009467:Neuromuscular Depolarizing Agents; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium