Functional Coupling of Voltage-Depengent L-Type Ca(superscript 2+) Current to Ca(superscript 2+)-Activated K(superscript +) Current in Pituitary GH3 Cells

Sheng-Nan Wu；Yuk-Keung Lo；Hui-Fang Li；Ai-Yu Shen

L-type Ca(superscript 2+) current ； Ca(superscript 2+)-activated K(superscript +) current ； GH3 cells

The Chinese Journal of Physiology

44卷4期（2001 / 12 / 31）

161 - 167

英文

Ca(superscript 2+)-activated K(superscript +) currents (I(subscript K(ca))) can contribute to action potential repolarization and after-hyperpolarization in GH3 cells. In this study, we examined how the activation of I(subscript K(Ca)) at the cellular level could be functionally coupled to Ca(superscript 2+) influx through L-type Ca(superscript 2+) channels. A 30-msec Ca(superscript 2+) influx step to 0 mV was found to exhibit substantial contribution of Ca(superscript 2+) influx through the activation of I(subscript (Ca,L)) to the activation of I(subscript K(Ca)). A bell-shaped relationship between the conditioning potentials and the integrated I(subscript K(Ca)) was observed, suggesting that the magnitude of integrated I(subscript Ca,L) correlates well with that of integrated I(subscript K(Ca)) in the same cell. A linear relationship of integrated I(subscript Ca,L) and integrated I(subscript K(Ca)) was found with a coupling ratio of 69±7. The value of the coupling ratio was unaffected by the presence of Bay K 8644 or nimodipine, although these compounds could effectively affect the amplitudes of both I(subscript K(Ca)) and I(subscript Ca, L). However, tetrandrine could decrease the coupling ratio. Paxilline or intracellular Ca(superscript2+) buffer with EGTA decreased the coupling ratio, while apamin had no effect on it. Interestingly, phorbol 12-myristate 13-acetate also reduced the coupling ratio significantly, whereas thapsigargin increased this value. Thus, the present study indicates that the activation of I(subscript K(Ca)) during brief Ca(superscript 2+) influx, which is inhibited by paxilline, is coupled to Ca(superscript 2+) influx primarily through the L-type channels. The selective modulation of I(subscript K(Ca)) by second messengers or Ca(superscript 2+) release from internal stores may affect the coupling efficiency and hence cellular excitability.