Ca 2+-activated K + channel blockers induce PKC modulated oscillatory contractions in guinea pig trachea

Abstract

Mechanisms underlying the Ca 2+-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 μM), a blocker of SK Ca, induced no contraction in guinea pig trachea and did not affect ChTX-induced oscillatory contractions. In Ca 2+ free solution, no ChTX-induced contraction was observed. Nifedipine (100 nM), a blocker of voltage-dependent Ca 2+ channels, and SK&F 96365 (10 μM), a blocker of capacitative Ca 2+ entry, completely abolished ChTX-induced oscillatory contractions. Ryanodine (1 μM) decreased the amplitude, but increased the frequency of the oscillatory contractions. Thapsigargin (1 μM) changed contractions from the oscillatory type to the sustained type. Moreover, the protein kinase C (PKC) inhibitor, bisindolylamaleimide I (1 μM), decreased the amplitude and frequency, but PKC activator, phorbol 12-myristate 13-acetate (1 μM), increased the frequency of oscillatory contractions. These results suggest that K Ca inhibitors-induced oscillatory contractions are initiated by Ca 2+ influx through L-type voltage-dependent Ca 2+ 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.