Ca2+-activated K+ channel blockers induce PKC modulated oscillatory contractions in guinea pig trachea.
Mechanisms underlying the Ca2+-activated K+ channel (K(Ca)) blockers-induced oscillatory contractions were investigated in guinea pig tracheal smooth muscle. The mean oscillatory frequencies induced by charybdotoxin (ChTX; 100 nM) and iberiotoxin (IbTX; 100 nM) were 9.8+/-0.8 (counts/h) and 8.0+/-1.3 (counts/h), respectively. Apamin (1 microM ), a blocker of SK(Ca), induced no contraction in guinea pig trachea and did not affect ChTX-induced oscillatory contractions. In Ca2+ free solution, no ChTX-induced contraction was observed. Nifedipine (100 nM), a blocker of voltage-dependent Ca2+ channels, and SK&F 96365 (10 microM), a blocker of capacitative Ca2+ entry, completely abolished ChTX-induced oscillatory contractions. Ryanodine (1 microM) decreased the amplitude, but increased the frequency of the oscillatory contractions. Thapsigargin (1 microM) changed contractions from the oscillatory type to the sustained type. Moreover, the protein kinase C (PKC) inhibitor, bisindolylamaleimide I (1 microM), decreased the amplitude and frequency, but PKC activator, phorbol 12-myristate 13-acetate (1 microM), increased the frequency of oscillatory contractions. These results suggest that K(Ca) inhibitors-induced oscillatory contractions are initiated by Ca2+ influx through L-type voltage-dependent Ca2+ channels. The ryanodine-sensitive calcium release channels in the sarcoplasmic reticulum may play an important role in maintaining the oscillatory contractions. Moreover, PKC activity modulates these oscillatory contractions.
Yagi
Yukihiro
Y
Department of Comparative Pathophysiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Kuwahara
Masayoshi
M
Tsubone
Hirokazu
H
D000818:Animals; D002118:Calcium / Q000502:physiology; D018999:Charybdotoxin / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology*; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors*; D011493:Protein Kinase C / Q000502:physiology*; D014132:Trachea / Q000502:physiology*
D010455:Peptides; D024681:Potassium Channels, Calcium-Activated; D018999:Charybdotoxin; C064719:iberiotoxin; D011493:Protein Kinase C; D002118:Calcium