Changes in Cytoplasmic Calcium Induced by Purinergic P_2x Receptor Activation in Vascular Smooth Muscle Cells and Sensory Neurons

Abstract

It is now widely accepted that ATP is an excitatory sympathetic co-transmitter (reviewed by Burnstock and Kennedy, 1986) which, on release generates fast excitatory junction potentials in arteries (Stjarne, 1986) and some other smooth muscles (Sneddon and Westfall, 1982). These contractile actions of ATP on smooth muscle appear to be due to activation of the P_2x subtype of purinoceptor (Burnstock and Kennedy, 1985) which gates a cation permeable channel. In sensory neurons (Krishtal et al., 1983), a very similar ATP receptor/channel also causes depolarization by the activation of inward currents. In vascular smooth muscle, ATP is generally thought to stimulate contraction by activating a mainly sodium permeable conductance that depolarizes the cell (Suzuki, 1985) and opens voltage-gated Ca²⁺ channels (Burnstock, 1988) allowing calcium entry. The advent of patch-clamp techniques has allowed detailed study of the ATP-activated channels in vascular smooth muscle revealing that the conductance is cation selective (Benham et al., 1987), and that the channels are closely coupled to the ATP receptor (Benham and Tsien, 1987). Results from current reversal potential measurements suggested that the channels are permeable to Ca²⁺ with a selectivity of three to one over Na⁺. Bearing in mind the much higher concentration of Na⁺ present in extracellular saline, the calculated Ca²⁺ influx is less than 10% of the total ATP activated current. However, permeation calculations are subject to error, especially for Ca²⁺ permeable channels where the strict conditions of the Goldman equation are not fulfilled (Tsien et al., 1987).