Differential oxygen sensitivity of calcium channels in rabbit smooth muscle cells of conduit and resistance pulmonary arteries.

Abstract

1. Calcium currents were recorded from smooth muscle cells dispersed from conduit and resistance rabbit pulmonary arteries. We tested the hypothesis that Ca2+ channel activity was regulated by environmental 02 tension.2. Conduit (proximal) and resistance (distal) myocytes differ in their Ca2P channel density and responses to low Po2. Ca2P current density in distal myocytes (20'7 + 7-4 pA pFY, n = 10)is almost twice the value in proximal myocytes (12-6 + 5-5 pA pF', n = 39). In proximal myocytes, the predominant response to reductions in P02 is inhibition of the calcium current (n = 12) at membrane potentials below 0 mV, whereas potentiation of current amplitude is observed in distal myocytes (n = 24). 3. Hypoxia also produces opposite shifts in the conductance-voltage relationships along the voltage axis. The average displacements induced by low P02 are +5 05 + 2-98 mV (n = 5) in proximal myocytes and -6-06 + 2-45 (n = 10) in distal myocytes.4. These findings demonstrate longitudinal differences in Ca2P channel density and 02 sensitivity in myocytes along the pulmonary arterial tree. These results may help to understand the differential reactivity to hypoxia of the pulmonary vasculature: vasodilatation in conduit arteries and vasoconstriction in resistance vessels.

Knockdown of stromal interaction molecule 1 attenuates store-operated Ca2+ entry and Ca2+ responses to acute hypoxia in pulmonary arterial smooth muscle

“…In our (53)(54)(55) previous studies of distal PASMC, nifedipine, an antagonist of L-type Ca 2ϩ channels, inhibited VOCE (11) and/or causing membrane depolarization (25,31,40,61). The former was reported in rabbit distal PASMC (11); however, this observation remains unconfirmed and its underlying mechanism unknown.…”

Relationship between membrane potential, delayed rectifier K+ currents and hypoxia in rat pulmonary arterial myocytes

“…Our experiments were also performed in the absence of extracellular Ca2 , thereby obviating the possibility of depolarization being mediated as a consequence of Ca2+ influx through voltage-activated Ca2+ channels. This is an important consideration since pulmonary arterial Ca2+ channels are known to be activated by hypoxia (Franco-Obreg6n & L6pez-Barneo, 1996), an effect which could account at least in part for the depolarization seen by others (Post et al 1992;Yuan et al 1993). Finally, no other studies have used cells isolated from small pulmonary arterial vessels.…”

Oxidant and redox signaling in vascular oxygen sensing mechanisms: basic concepts, current controversies, and potential importance of cytosolic NADPH

“…Using whole cell patch-clamp technique, Franco-Obregon and coworkers (27,28) showed that rabbit PASMC voltage-gated Ca 2ϩ channels opened and closed by alternating a hypoxia-reoxygenation stimulus, respectively. They also demonstrated that resistance and conduit PASMC voltage-gated Ca 2ϩ channels were opened and closed by exposure to reductions in PO 2 (26), thus indicating that either the expression or regulation of L-type Ca 2ϩ channels was different in conduit arteries that show minimal contraction to hypoxia compared with resistance pulmonary artery smooth muscle that generally contract to hypoxia. Additionally, some of the latest data also suggest that hypoxia stimulates opening of receptor-operated Ca 2ϩ channels and modulates Ca 2ϩ release from the ryanodinesensitive Ca 2ϩ stores that mediate HPV (76).…”