Modulation of Voltage-Gated Ca²⁺ Channels by O₂ Tension

Abstract

Physiological adaptations to changes in oxygen availability are expressed in several tissues, which facilitate survival in situations of oxygen rarity, or hypoxia. These physiological responses to hypoxia are mediated by the arterial chemoreceptors which have classically been treated as synonymous with the carotid bodies (for a review see González et al, 1992) but which, in a broader sense, should also include the arterial smooth muscle cell layer (Sparks, 1980; Wadsworth, 1994). Among the acute responses to hypoxia are hyperventilation and active changes in vascular resistance controlling local circulation. Combined these physiological responses to hypoxia act to increase the uptake and ventilation of oxygen within the lungs, as well as, to better irrigate hypoxic regions of the body. Hyperventilation ensues from the activity of peripheral chemoreceptors located in the carotid and aortic bodies which transduce changes in blood oxygen content into neurosecretory activity. Chemotransduction in the carotid body has been attributed, among other factors, to the existence in glomus cells of K⁺ channels regulated by blood PO₂ (López-Barneo et al, 1988; Delpiano & Hescheler, 1989). Thus, similar O₂-modulated ion channels may also be present in other tissues responsive to alterations in PO₂. We have recently demonstrated the existence of O₂-modulated Ca²⁺ channels in vascular smooth muscle cells where they may play a key role in the vasomotor responses to hypoxia (Franco-Obregón et al, 1995; Franco-Obregón & López-Barneo, 1996). A similar effect of PO₂ on the voltage-gated Ca²⁺ channels of the chemoreceptive cells of the rabbit carotid body has also been recently found (Montoro et al, 1996). Since in both preparations (glomus cells and vascular smooth muscle) the transduction of the hypoxic stimulus requires the modulation of cytosolic Ca²⁺ levels, the O₂-sensitive Ca²⁺ channels described here are well suited to confer chemoreceptive properties to these tissues.