Ion channel modifying agents influence the electrical activity generated by canine intrinsic cardiac neurons in situ.
This study was designed to establish whether agents known to modify neuronal ion channels influence the behavior of mammalian intrinsic cardiac neurons in situ and, if so, in a manner consistent with that found previously in vitro. The activity generated by right atrial neurons was recorded extracellularly in varying numbers of anesthetized dogs before and during continuous local arterial infusion of several neuronal ion channel modifying agents. Veratridine (7.5 microM), the specific modifier of Na+-selective channels, increased neuronal activity (95% above control) in 80% of dogs tested (n = 25). The membrane depolarizing agent potassium chloride (40 mM) reduced neuronal activity (43% below control) in 84% of dogs tested (n = 19). The inhibitor of voltage-sensitive K+ channels, tetraethylammonium (10 mM), decreased neuronal activity (42% below control) in 73% of dogs tested (n = 11). The nonspecific potassium channel inhibitor barium chloride (5 mM) excited neurons (47% above control) in 13 of 19 animals tested. Cadmium chloride (200 microM), which inhibits Ca2+-selective channels and Ca2+-dependent K+ channels, increased neuronal activity (65% above control) in 79% of dogs tested (n = 14). The specific L-type Ca2+ channel blocking agent nifedipine (5 microM) reduced neuronal activity (52% blow control in 72% of 11 dogs tested), as did the nonspecific inhibitor of L-type Ca2+ channels, nickel chloride (5 mM) (36% below control in 69% of 13 dogs tested). Each agent induced either excitatory or inhibitory responses, depending on the agent tested. It is concluded that specific ion channels (I(Na), I(CaL), I(Kv), and I(KCa)) that have been associated with intrinsic cardiac neurons in vitro are involved in their capacity to generate action potentials in situ.
Thompson
G W
GW
Department of Physiology and Biophysics, Dalhousie University, Halifax, NS, Canada.
Horackova
M
M
Armour
J A
JA
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D020746:Calcium Channels, L-Type / Q000187:drug effects; D004285:Dogs; D004594:Electrophysiology; D005260:Female; D006321:Heart / Q000294:innervation*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007261:Infusions, Intra-Arterial; D007473:Ion Channels / Q000187:drug effects*; D008297:Male; D009474:Neurons / Q000187:drug effects*; D009532:Nickel / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects
D020746:Calcium Channels, L-Type; D007473:Ion Channels; D015222:Sodium Channels; C022838:nickel chloride; D009532:Nickel