Effects of Ca2+ and K+ channel blockers on nerve impulses recorded from guinea-pig postganglionic sympathetic nerve terminals.
1. A focal extracellular suction electrode was used to investigate the contributions of K+ and Ca2+ currents to the nerve impulse recorded from sympathetic nerve terminals innervating the guinea-pig vas deferens in vitro. 2. Perfusing the electrode with Cd2+ (0.1-0.5 mM) had little effect on the configuration of the nerve impulse. 3. Perfusing the electrode with Ba2+ (1-3 mM) caused the appearance of a second negative-going component of the nerve impulse. Local application of Cd2+ (0.1 mM) had little affect on this component of the nerve impulse. 4. Perfusing the electrode with 4-aminopyridine (4-AP) and/or tetraethylammonium (TEA) caused the appearance of a second negative-going component of the nerve impulse. This component has been termed the late negative-going component (LNC). 5. The LNC produced by local application of 1 mM 4-AP and 10 mM TEA was not changed when the solution perfusing the electrode contained no added Ca2+, 10 mM Ca2+ or omega-conotoxin GVIA (0.1 microM). Perfusion of the electrode with Cd2+ (0.1 mM) reduced the amplitude and slowed the time course of the LNC. 6. The LNC was markedly inhibited when the organ bath was perfused with TEA (10 mM) or 4-AP and TEA (1 and 10 mM, respectively). In some experiments the LNC was completely abolished. 7. The LNC was reduced in amplitude and slowed in time course when the solution perfusing the organ bath contained no added Ca2+. A similar effect on the LNC was observed when the solution perfusing the organ bath contained omega-conotoxin GVIA (0.1 microM), charybdotoxin (0.05 microM) or low concentrations of TEA (0.3-1 mM) or Ba2+ (10-500 microM). 8. Bath application of the alpha 2-adrenoceptor agonist clonidine (0.1-0.3 microM) did not detectably change the LNC. 9. The results demonstrate that the LNC produced by the local application of K+ blockers is due primarily to K+ efflux from sites outside the recording electrode and that a part of the change in conductance that underlies this component is due to opening of Ca(2+)-activated K+ channels. The failure to detect an effect of clonidine on the LNC suggests that activation of presynaptic alpha 2-adrenoceptors does not change either the K+ or the Ca2+ conductance of the nerve terminals.
Brock
J A
JA
Faculty of Medicine and Health Sciences, University of Newcastle, Callaghan, NSW, Australia.
Cunnane
T C
TC
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D006168:Guinea Pigs; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects*; D026902:Potassium Channel Blockers; D013564:Sympathetic Nervous System / Q000187:drug effects*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D002121:Calcium Channel Blockers; D026902:Potassium Channel Blockers; D013757:Tetraethylammonium Compounds; D002104:Cadmium; D001464:Barium; D019789:Tetraethylammonium; D015761:4-Aminopyridine; D002118:Calcium