Quantal and non-quantal current and potential fields around individual sympathetic varicosities on release of ATP

The electrical phenomena that occur at sympathetic varicosities due to the release of ATP include spontaneous and evoked excitatory junction potentials (SEJPs and EJPs; recorded with an intracellular electrode) as well as fast and slow excitatory junctional currents (EJCs; recorded with a loose-patch electrode placed over varicosities). The electrical analysis of these transients is hampered by lack of a detailed theory describing how current and potential fields are generated upon the release of a quantum of ATP. Here, we supply such a theory and develop a computational model for the electrical properties of a smooth muscle syncytium placed within a volume conductor, using a distributed representation for the individual muscle cells. The amplitudes and temporal characteristics of both SEJPs and fast EJCs are predicted by the theory, but those of the slow EJCs are not. It is shown that these slow components cannot arise as a consequence of propagation of fast quantal components from their site of origin in the muscle syncytium to the point of recording. The possibility that slow components arise by a mechanism of transmitter secretion that is different from quantal release is examined. Experiments that involve inserting peptide fragments of soluble N-ethylmaleimide-sensitive fusion attachment protein (alpha-SNAP) into varicosities, a procedure that is known to block quantal release, left the slow component of release unaffected. This work provides an internally consistent description of quantal potential and current fields about the varicosities of sympathetic nerve terminals and provides evidence for a non-quantal form of transmitter release.