| Abstract: | Photon activation of the halogenated fluorescein derivative erythrosine caused a marked calcium-dependent contraction of the smooth muscle cells of the guinea-pig taenia coli superfused in vitro. Neither high intensity illumination alone (up to 5 X 10(4) lux) nor erythrosine alone (up to 2 X 10(-4) M) altered the tone of the taenia or its ability to respond to carbachol (5 X 10(-5) M); photo-irradiation of erythrosine before tissue contact was also ineffective. The magnitude of the photodynamic contraction was dependent upon the concentration of erythrosine, the intensity and wavelength of the incident light, and the presence of oxygen; indirect effects via neurotransmitter release or cyclo-oxygenase activation were specifically excluded. The photodynamic response was blocked by zero-[Ca]o and addition of EGTA (1 mM) but not by omission of [Mg]o or a decrease in [Cl]o or [Na]o. D600 (methoxyverapamil) 10(-5) M, or a ten fold increase in [Mg]o, to 11.3 mM, partly inhibited the photodynamic contraction at low, but not high, light intensities. These observations are consistent with the following sequence of events: (i) photo-activation of the erythrosine molecule, (ii) the generation of highly reactive singlet oxygen, (iii) local peroxidation of cell membrane proteolipid, (iv) increased membrane permeability to Ca2+, (v) the influx of Ca2+ and, (vi) muscle contraction. It is concluded that the photodynamic action of erythrosine presents a novel method for modulation of membrane calcium permeability, and hence [Ca]i, not only in smooth muscle but possibly in other cells as well, e.g., secretory, epithelial and myocardial cells. |
