Effect of voltage and cyclic AMP on frequency of slow‐wave‐type action potentials in canine colon smooth muscle.

Abstract

SUMMARY1. A non-L-type calcium conductance is involved in the generation of the initial part of the slow-wave-type action potential in colonic smooth muscle. The present study addresses the question whether this conductance is voltage or metabolically activated.2. Current-induced hyperpolarization increased frequency and amplitude of slow waves measured in Krebs solution.3. The upstroke potential was 'isolated' from the slow wave by superfusion with 'glucamine-nitrendipine' Krebs solution (NaCl was replaced by glucamine, nitrendipine was added).4. Hyperpolarization up to -100 mV did not affect the upstroke potential frequency and increased its amplitude. Only hyperpolarization further than -100 mV decreased the frequency < 20%, and reduced the amplitude < 20%.5. Depolarization did not affect the upstroke potential frequency. 6. Forskolin, but not 1,9-dideoxyforskolin dramatically decreased the upstroke potential frequency, without affecting other parameters including the resting membrane potential.7. The effect of forskolin was mimicked by dibutyryl cyclic AMP, 8-bromo-cyclic AMP and 3-isobutyl-1-methylxanthine (IBMX), but not extracellular cyclic AMP.8. The upstroke potential could not be evoked by depolarizing pulses after inhibition of activity by forskolin.9. The effect of forskolin could be reversed by the calcium ionophore A23187. 10. In summary, voltage changes up to -40 mV and down to -100 mV do not, but changes in intracellular cyclic AMP do affect the frequency of the upstroke potential.11. It is likely that intracellular metabolic activity, which may include cyclic AMP but not a voltage change, activates the conductance responsible for the generation of the upstroke potential.

Properties of spontaneous depolarizations in circular smooth muscle cells of rabbit urethra

“…These cells are connected by numerous gap junctions to the smooth muscle. There have been a number of proposals regarding the generation of slow waves including: generation involving sodium pump activity (Connor et al, 1974), a Na'-Ca2" exchange mechanism (Tomita, 1981), metabolic activity (Huizinga et al, 1991) or a cardiac-like pacemaker cycle involving low threshold, voltage-dependent Ca2" channels (Lee & Sanders, 1993;Publicover, 1994). 1 Author for correspondence.…”

T-type Ca2+ channels in non-vascular smooth muscles

“…[41]. The model explains a number of features, including a role for the inward Ca 2+ current activated at negative potentials, the dependence of pacemaking on extracellular and on intracellular metabolic activity [42,43].…”

Relaxation Patterns of Human Gastric Corporal Smooth Muscle by Cyclic Nucleotides Producing Agents

“…Since these stimulators are known to inhibit slow wave and produce hyperpolarization, then suppressing contraction, it inhibits phasic contraction and basal tone in GI tract (Andersson and Nilsson, 1972;Jin et al, 1993;Smith et al, 1993). These findings imply that cyclic nucleotide activators such as FSK and SNP play an inhibitory role for basal tone as well as spontaneous contraction in human stomach (Huizinga et al, 1991;Ozaki et al, 1992;Jin et al, 1993;Smith et al, 1993;Kim et al, 2006;Kim and Perrino, 2007).…”

“…β-Adrenergic nerve and VIP containing neurons in myenteric plexus, which project to the smooth muscle layers, have been reported to exist in the gut, and their stimulation inhibits slow wave and contraction via increasing cAMP and/or cGMP (Andersson and Nilsson, 1972;Jin et al, 1993;Smith et al, 1993). Furthermore, FSK and SNP, cyclic nucleotide (cAMP and cGMP) activators, have also been shown to inhibit electrical and contractile activity of GI smooth muscle (Huizinga et al, 1991;Ozaki et al, 1992;Jin et al, 1993;Smith et al, 1993;Kim et al, 2006;Severi et al, 2006). In the present study, we found the inhibitory effect of ISO in human stomach: ISO inhibited spontaneous contraction and basal tone in a reversible manner (Fig.…”

“…Especially, NO is recognized as a neurotransmitter of nonadrenergic non-cholinergic (NANC) nerves in the myenteric plexus throughout the GI tract and is responsible for gastric receptive relaxation (Ozaki et al, 1992;Jin et al, 1993;Smith et al, 1993;Tonini et al, 2000). In addition, sodium nitroprusside (SNP), known NO-releasing compound, is reported to stimulate guanylate cyclase and then increase intracellular guanosine 3',5'-cyclic monophosphate (cGMP) levels, while forskolin (FSK) to stimulate adenylate cyclase and then adenosine 3',5'-cyclic monophosphate (cAMP) levels in many smooth muscles, including GI tract (Katsuki et al, 1977;Huizinga et al, 1991;Ozaki et al, 1992;Jin et al, 1993;Smith et al, 1993;Severi et al, 2006). Therefore, the resultant activation of cAMP-dependent protein kinase A (PKA) and cGMP-dependent protein kinase G (PKG) seems to be linked to the inhibitory effects of FSK, ISO and SNP (Schultz et al, 1977;Jin et al, 1993;Smith et al, 1993).…”