Hypoxia inhibits the recombinant alpha 1C subunit of the human cardiac L‐type Ca2+ channel.

Abstract

1. Whole-cell patch clamp recordings were used to investigate the effects of hypoxia on recombinant human L-type Ca2P channel a1c subunits stably expressed in human embryonic kidney (HEK 293) cells.2. Ca2P channel currents were reversibly inhibited by hypoxia (Po2 < 90 mmHg). The degree of inhibition depended on the charge carrier used, Ca2+ currents being more 02 sensitive than Ba2+ currents. 3. Hypoxic inhibition of Ca2+ channel currents was more pronounced at lower activating membrane potentials (< +30 mV), and was associated with a slowing of activation kinetics. Current inactivation and deactivation were unaffected by hypoxia. 4. Since hypoxia similarly regulates native L-type Ca2+ channels in vascular smooth muscle cells, our results suggest that hypoxic regulation of L-type Ca2+ channels arises from modification of structural features of the a1 subunit common to cardiac and smooth muscle L-type channels.

Acid‐evoked quantal catecholamine secretion from rat phaeochromocytoma cells and its interaction with hypoxia‐evoked secretion

“…Such a scheme must remain speculative at present, since there is no detailed information concerning the differential effects of pH on different classes of Ca¥ channel within a given preparation. Furthermore, although hypoxia is known to regulate L_type Ca¥ channels (Fearon et al 1997), its effects on other classes of Ca¥ channel remain completely unexplored. Hypoxia and acidity have long been known to be greater than additive in their ability to increase afferent chemosensory nerve activity, since the slope of the linear relationship between COµÏacidosis and nerve activity increases with increasing degrees of hypoxia (Fitzgerald & Parks, 1971;Lahiri & Delaney, 1975).…”

General – Ion Channels

“…Importantly, residual currents recorded following MTSEA Journal of Physiology (1998) 506.P treatment were reversibly inhibited by hypoxia (Po, ca 20 mmHg) by 28'6 ± 3'8 % (n = 12), a degree of inhibition that was not significantly different from that seen in untreated cells (Fearon et al 1997). However, following pCMBS treatment, the same degree of hypoxia was unable to reduce currents further (n = 8).…”

“…Agents that reduce or oxidize sulphydryl-containing residues in ferret ventricular myocyte Ca2+ channels have profound effects on channel function (Campbell et al 1996). We have previously shown that hypoxia inhibits recombinant human cardiac L-type Ca2+ channel a lC subunits stably expressed in HEK 293 cells (Fearon et al 1997). Here we have investigated whether sulphydrylcontaining residues may be involved in this action of hypoxia.…”

“…Here we have investigated whether sulphydrylcontaining residues may be involved in this action of hypoxia. Whole-cell Ca 2 + channel currents were recorded as previously described (Fearon et al 1997) also reduced lea by 56'9 ± 4'1 % (n = 9, P < 0'0001). In both cases, inhibition could be reversed by dithiothreitol (DTT, 2 mM).…”

Developmental Absence of the O2 Sensitivity of L-Type Calcium Channels in Preterm Ductus Arteriosus Smooth Muscle Cells Impairs O2 Constriction Contributing to Patent Ductus Arteriosus

“…␣1c is the putative O 2 -sensing subunit, and work by Fearon et al (29,30) indicate that auxiliary subunits are not necessary for O 2 sensing in the human cardiac Ca L . Several splice variants of the ␣1 subunits exist.…”