CELL-MEMBRANE STRETCH IN OSTEOCLASTS TRIGGERS A SELF REINFORCING CA2+ENTRY PATHWAY

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.