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 neurona l ion channels influence the behavior of mammalian intrinsic cardiac neuron s in situ and, if so, in a manner consistent with that found previously in vitro. The activity generated by right atrial neurons was recorded extracel lularly in varying numbers of anesthetized dogs before and during continuou s local arterial infusion of several neuronal ion channel modifying agents. Veratridine (7.5 mu M), the specific modifier of Na+-selective channels, i ncreased neuronal activity (95% above control) in 80% of dogs tested (n = 2 5). The membrane depolarizing agent potassium chloride (40 mM) reduced neur onal activity (43% below control) in 84% of dogs tested (n = 19). The inhib itor of voltage-sensitive K+ channels, tetraethylammonium (10 mM), decrease d neuronal activity (42% below control) in 73% of dogs tested (n = 11). The nonspecific potassium channel inhibitor barium chloride (5 mM) excited neu rons (47% above control) in 13 of 19 animals tested. Cadmium chloride (200 mu M), which inhibits Ca2+-selective channels and Ca2+-dependent K+ channel s, increased neuronal activity (65% above control) in 79% of dogs tested (n = 14). The specific L-type Ca2+ channel blocking agent nifedipine (5 mu M) 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 m M) (36% below control in 69% of 13 dogs tested). Each agent induced either excitatory or inhibitory responses, depending on the agent tested. It is co ncluded 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 th eir capacity to generate action potentials in situ.