Mechanisms underlying the electrical and mechanical responses of the guinea‐pig internal anal sphincter to field stimulation and to drugs

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Abstract
1 The electrical membrane characteristics and the response of the circular muscle of the guinea-pig internal anal sphincter (i.a.s.) to field stimulation were studied in vitro using intracellular microelectrodes and conventional mechanical recording techniques. 2 The i.a.s. developed its own tone (3–4 g), following initial stretch (1 g) and spontaneous spike potentials were evident. In the absence of spike potentials, tone declined and disappeared. Tone was not significantly reduced by phentolamine (1 × 10−6 M). The resting membrane potential, measured between spontaneous spike potentials, was − 45 ± 3.0 mV (n = 224); the space constant (Λ) was 1.13 ± 0.1 mm (n = 13). Spikes usually overshot by approximately 15 mV. 3 The frequency of spike potential discharge (1–3 Hz) varied with the degree of membrane depolarization, being increased in K+-rich and decreased in K+-deficient solutions or by the presence of Mn2+. It was not significantly affected by Cl−-withdrawal but was increased in Na+-deficient solutions with or without tetrodotoxin (TTX; 1 × 10−6 M). 4 Field stimulation (1–20 Hz, 0.5 ms, supramaximal voltage) produced inhibitory junction potentials (i.j.ps) and relaxed tone; at high frequencies (50 Hz or greater), contractions were observed but excitatory junction potentials (e.j.ps) were not. I.j.ps and relaxations were inhibited by apamin (1 × 10−6M), TTX (1 × 10−6M) but not by atropine (1 × 10−6M), phentolamine (1 × 10−6M) or hexamethonium (1 × 10−6M). 5 I.j.ps were reduced by hyperpolarization and enhanced by depolarization of the membrane by current pulses (15 s). The mean equilibrium potential for the i.j.p. was − 94 mV (correlation coefficient, γ = 0.71, n = 5, p < 0.001). I.j.ps were enhanced in K+-deficient solutions and reduced in K+-rich solutions. Together these results suggest that the i.j.p. is mediated by an increased GK. The absence of [Ca2+]o or the presence of Mn2+ (2 mM) abolished the i.j.p.; in contrast Na+-deficient or Cl−-free solutions were ineffective in this respect. 6 Tetraethylammonium (5–50 mM) abolished the i.j.p.; the accompanying relaxation was reduced by about 80%. The major aspect of the relaxation to nerve stimulation is mediated by membrane hyperpolarization.