Many cell types respond to mechanical membrane perturbation with intra
cellular Ca2+ responses. Stretch-activated (SA) ion channels may be in
volved in such responses. We studied the occurrence as well as the und
erlying mechanisms of cell membrane stretch-evoked responses in fetal
chicken osteoclasts using separate and simultaneous patch-clamp and Ca
2+ imaging measurements. In the present paper, evidence is presented s
howing that such responses involve a self-reinforcing mechanism includ
ing SA channel activity, Ca2+-activated K+ (K-Ca) channel activity, me
mbrane potential changes and local and general intracellular Ca2+ ([Ca
2+](i)) increases. The model we propose is that during membrane stretc
h, both SA channels and K-Ca channels open at membrane potential value
s near the resting membrane potential. SA channel characterization sho
wed that these SA channels are permeable to Ca2+. During membrane stre
tch, Ca2+ influx through SA channels and hyperpolarization due to K-Ca
channel activity serve as positive feedback, leading ultimately to a
Ca2+ wave and cell membrane hyperpolarization. This self-reinforcing m
echanism is turned off upon SA channel closure after cessation of memb
rane stretch. We suggest that this Ca2+ entry mechanism plays a role i
n regulation of osteoclast activity.