Muscarinic suppression of Ca2+-dependent K current in colonic smooth muscle

Abstract

Acetylcholine (ACh) increases the amplitude and duration of colonic electrical slow waves. This suggests that ACh either increases an inward current or suppresses an outward current. The latter hypothesis was tested in whole cell voltage-clamp experiments performed on freshly dispersed smooth muscle cells from canine proximal colon. Addition of ACh (10(-5) M) to solutions bathing cells reduced time-dependent outward currents elicited by depolarizing test pulses in the range of -45 to +30 mV. Analysis of tail currents showed that ACh caused a 10- to 15-mV positive shift in voltage-dependent activation. When cells were pretreated with 10(-6) M nifedipine to abolish the Ca2+-dependent component of the outward current, the reduction of outward current by ACh was blocked. Single-channel experiments were performed to determine whether ACh had a direct effect on Ca2+-activated K channels. ACh, 10(-5) M, added to bath and pipette solutions caused a positive shift in voltage-dependent activation in on-cell experiments. This effect of ACh on Ca2+-activated K channels provides a mechanism for the effects of muscarinic, excitatory stimulation of circular muscle of the colon.

Muscarinic Agonist-Mediated Heterologous Desensitization in Isolated Ileum Requires Activation of Both Muscarinic M2 and M3 Receptors

“…It is well known that Ca 2ϩ -activated K ϩ channels are abundantly expressed in smooth muscle and are activated indirectly upon muscarinic stimulation due to the rise in intracellular Ca 2ϩ (Cole et al, 1989;Kume et al, 1992;Wade and Sims, 1993;Carl et al, 1995). These channels represent an inhibitory feedback mechanism that limits contraction and Ca 2ϩ influx, and this inhibitory action may be responsible for preventing heterologous desensitization caused activation of M 3 receptors only.…”

Mechanisms of L‐NG nitroarginine/indomethacin‐resistant relaxation in bovine and porcine coronary arteries

“…Thus, pertussis toxin either interferes with the formation of EDHF directly or, more likely, prevents the effect of EDHF on smooth muscle K+ channels. The involvement of pertussis toxin-sensitive G protein in muscarinic receptor-mediated inhibition of Ca2'-activated K+ channels has been described in vascular smooth muscle cells (Kume & Kotlikoff, 1991), airway smooth muscle cells (Kume et al, 1995) and colonic smooth muscle (Cole et al, 1989). Furthermore G protein-regulated K+ channels have been shown in the epithelial-cell line (Hemada et al, 1993), cortical collecting duct cells (Suzuki et al, 1994), adrenal chromaffin cells (Cannon et al, 1994) and rabbit atrai (Ray & Macheod, 1994).…”

Differential Coupling of Muscarinic M1, M2, and M3 Receptors to Phosphoinositide Hydrolysis in Urinary Bladder and Longitudinal Muscle of the Ileum of the Mouse

“…Likewise, the coupling of M 2 receptors to inhibition of adenylyl cyclase is consistent with its role in mediating an inhibition of the relaxant effect of agents that increase cAMP levels (Thomas et al, 1993;Sawyer and Ehlert, 1998). Activation of M 2 receptor has also been shown to mediate an increase in a nonselective cationic conductance (Bolton, 1979) and an inhibition of Ca 2ϩ -activated K ϩ channels (Cole et al, 1989), which might explain how M 2 receptors mediate an enhancement in contractions elicited by the M 3 receptor.…”