Ca2+-induced Ca2+ release activates K+ currents by a cyclic GMP-dependent mechanism in single gastric smooth muscle cells

The participation of sarcoplasmic reticulum Ca2+ release channels in the activation of Ca2+-sensitive K+ currents (I-K(Ca)) by cyclic dibutyryl GMP was investigated in smooth muscle cells from the circular layer of guinea-pig gastric fundus. All experiments were performed in the presence of 3 mu M nicardipine into the bath and low Ca2+ buffering capacity of the pipette-filling solution (pCa 7.4). Ruthenium red (10 mu M) as well as its combination with 10 mu M heparin abolished the cyclic GMP-induced activation of I-K(Ca), while 10 mu M heparin remained ineffective. Ryanodine (10 mu M) and the subsequently added 1 mu M thapsigargin induced a relatively small increase in I-K(Ca) amplitudes. The addition of 10 mu M ryanodine to 1 mu M thapsigargin-containing bath solution caused a vast increase in I-K(Ca). It is hypothesyzed that protein kinase G-induced vectorial Ca2+ flux from the cell bulk and sarcoplasmic reticulum Ca2+ stores toward the plasma membrane is realized by a spontaneous Ca2+-induced Ca2+ release from a superficially situated Ca2+ store.