Intracellular electrical and contractile responses to sympathetic nerve trunk stimulation (NTS) and transmural electrical field stimulation (TMS) were compared in the guinea-pig mesenteric artery in vitro. 2. Step increases in voltage with NTS gave rise to excitatory junctional potentials (EJPs) which reached a plateau amplitude of 5-10 mV, whereas with TMS larger amplitude EJPs and sometimes action potentials were obtained. 3. EJPs of equal amplitude (1-7 mV) elicited with TMS and NTS had the same rise time, duration and decay half-time. 4. Slow depolarization obtained with repetitive stimulation was significantly greater in amplitude with TMS than with NTS. 5. Equal amplitude EJPs were obtained throughout the preparation with NTS. With TMS, the amplitude of responses declined substantially with distance from the stimulating electrodes. 6. Tetrodotoxin (TTX) completely blocked EJPs, slow depolarization and contraction with NTS; however, with TMS a TTX-resistant component was observed. The TTX-resistant response to TMS was abolished in the presence of a low-Ca2+ superfusion solution but was not affected by endothelium removal. 7. Phentolamine or prazosin abolished slow depolarization but not EJPs with NTS or TMS. Prazosin abolished contraction with NTS and reduced but did not abolish contraction with TMS. 8. alpha, beta-Methylene ATP abolished EJPs with NTS, whereas with TMS only EJPs obtained with low stimulus intensities were abolished. alpha, beta-Methylene ATP did not block contraction with either NTS or TMS. 9. Combined TTX, prazosin and alpha, beta-methylene ATP abolished EJPs initiated with TMS at all but the highest stimulus intensities (12-20 V, 0.3 ms duration). 10. It is concluded that responses obtained with NTS can be reliably attributed to the release of transmitter by the conduction of action potentials in paravascular nerves, whereas activation by TMS is a more complex phenomenon dependent upon stimulus strength and probably involving multiple forms of activation.
