Contribution of chloride conductance increase to slow EPSC and tachykinin current in guinea‐pig myenteric neurones.

Abstract

1. Single electrode voltage clamp recordings were obtained from myenteric neurones of guinea-pig ileum in vitro. Slow excitatory postsynaptic currents (sEPSCs) were elicited by focal stimulation of interganglionic nerve strands in twenty-four of thirty neurones more than 30 min after impalement. In seventeen of twenty-four neurones, sEPSCs were associated with a conductance decrease and reversed polarity at -96 + 3 mV (near the reversal potential for potassium, EK); this response was due to inhibition of resting potassium conductance, gK. In seven of twenty-four neurones, there was either no net conductance change or a biphasic conductance change during the sEPSC; a reversal potential for peak currents could not be determined. 2. Application of senktide (3/uM), a neurokinin-3 receptor agonist, caused an inward current in forty-one of fifty-three neurones more than 30 min after impalement. In twenty of forty-one neurones, senktide-induced currents were due to inhibition of resting gK. In eleven of forty-one neurones there was either no net conductance change or a biphasic conductance change; a reversal potential for peak currents could not be determined. In ten out of forty-one neurones, senktide-induced currents were associated with a conductance increase (ginc); the estimated reversal potential was -17 + 3 mV.3. Application of forskolin (1 ,lM) caused an inward current that occluded the decrease in gK caused by senktide and the sEPSC. In neurones in which sESPCs and senktide responses were associated with an unclear or biphasic conductance change, forskolin did not reduce the peak current and residual currents were usually associated with a gin, 4. In neurones in which senktide-induced currents were associated with a gin, reducing extracellular Cl-to 13 mm reduced senktide-induced currents by 79%. Reducing extracellular Na+, or adding tetraethylammonium (TEA, 50 mM), cobalt (2 mM) or picrotoxin (30 ,lM) did not change senktide-induced currents. The chloride transport/ channel blockers niflumic acid and mefenamic acid (both at 100 /SM) blocked senktideinduced currents. It was concluded that senktide increases chloride conductance (gcl).5. Chord conductance measurements made between -70 and -90 mV during sEPSCs were used to determine the contribution of an increase in gcl to sEPSCs. These measurements indicated that the peak sEPSC is composed of a 90% decrease in g9 and a 10% increase in gcl. Similar data were obtained from measurements made during senktide responses.It was concluded that senktide-induced currents and sEPSCs are due to a concurrent decrease in g9 and an increase in gcl in a subset of myenteric neurones.

Substance P-Mediated Modulation of Pacemaker Properties in the Mammalian Respiratory Network

“…SP activates voltage-dependent Ca 2ϩ channels, voltage-dependent K ϩ conductances, Cl Ϫ currents, Ih currents, voltage-dependent Na ϩ channels, and nonselective cationic channels (Adams et al, 1983;Stanfield et al, 1985;Bley and Tsien, 1990;Shen and North, 1992;Bertrand and Galligan, 1994;Aosaki and Kawaguchi, 1996). In most neurons, SP depolarizes membrane potential by decreasing resting K ϩ conductances (Akasu et al, 1996;Lepre et al, 1996;Ptak et al, 2000;Yasuda et al, 2001).…”

Actions of Substance P on Rat Neostriatal NeuronsIn Vitro

“…An involvement of Cl Ϫ conductance is also unlikely (Bertrand and Galligan, 1994), because the equilibrium potential for the Cl Ϫ ions would be less than Ϫ52 mV, which is close to the resting membrane potential of the neurons, assuming that the ion concentrations of the cells become almost equal to that of the patch-pipette solution. Although our experiments by no means excluded the possible blocking actions of SP on channels such as K ϩ and Ca 2ϩ at the suprathreshold levels, our findings strongly imply that the SP-induced TTXinsensitive cation current accounts for virtually all of the inward current at rest in the large aspiny interneurons.…”

“…Electrophysiological studies on neurons in the other brain areas have shown that SP modulates several ionic conductances, and that the ionic mechanisms of SP actions differ considerably among neuronal types (Adams et al, 1983;Stanfield et al, 1985;Bley and Tsien, 1990;Shen and North, 1992;Bertrand and Galligan, 1994).…”

Effects of PGE2 in guinea pig colonic myenteric ganglia

“…Previous investigations have determined that NK 1 and NK 3 receptors mediate prolonged depolarizations in the myenteric plexus of the intestine and that tachykinins likely contribute to slow EPSPs in myenteric neurons (1,25,26). Because the result of the experiments in the presence of TTX indicated that a component of the PGE 2 -mediated depolarization may be indirect and due to release of neuroactive compounds from nearby nerve terminals, additional experiments were conducted to investigate a possible role of tachykinins in the generation of the indirect or presynaptic effects of PGE 2 observed in myenteric AH cells.…”