Two Ca²⁺ entry pathways mediate InsP₃‐sensitive store refilling in guinea‐pig colonic smooth muscle

Abstract

Sarcolemma Ca2+ influx, necessary for store refilling, was well maintained, over a wide range (‐70 to + 40 mV) of membrane voltages, in guinea‐pig single circular colonic smooth muscle cells, as indicated by the magnitude of InsP3‐evoked Ca2+ transients. This apparent voltage independence of store refilling was achieved by the activity of sarcolemma Ca2+ channels some of which were voltage gated while others were not. At negative membrane potentials (e.g. ‐70 mV), Ca2+ influx through channels which lacked voltage gating provided for store refilling while at positive membrane potentials (e.g. +40 mV) voltage‐gated Ca2+ channels were largely responsible. Sarcolemma voltage‐gated Ca2+ currents were not activated following store depletion. Removal of external Ca2+ or the addition of the Ca2+ channel blocker nimodipine (1 μM) inhibited store refilling, as assessed by the magnitude of InsP3‐evoked Ca2+ transients, with little or no change in bulk average cytoplasmic Ca2+ concentration. One hypothesis for these results is that the store may refill from a high subsarcolemma Ca2+ gradient. Influx via channels, some of which are voltage gated and others which lack voltage gating, may permit the establishment of a subsarcolemma Ca2+ gradient. Store access to the gradient allows InsP3‐evoked Ca2+ signalling to be maintained over a wide voltage range in colonic smooth muscle.

Cyclic ADP-ribose increases Ca2+ removal in smooth muscle

“…1Aa) and by photolysis of caged 25 µM InsP3 (∆F/F0=1.5±0.1, n=9, P<0.001; Fig. 1Ab) (McCarron et al, 2000). By contrast, photolysis of 50 µM caged cADPR did not increase [Ca 2+ ]c (∆F/F0=0.1±0.0, n=9, P>0.05; Fig.…”

Very low-frequency blood pressure variability depends on voltage-gated L-type Ca2+channels in conscious rats

“…However, the highest dose of nifedipine (5 mg⅐100 l Ϫ1 ⅐h Ϫ1 ) reduced LF blood pressure variability to the same residual noise level as ganglionic blockade. We suggest that prolonged application of L-type Ca 2ϩ channel blockers at high doses eliminates sympathetic modulation of vascular tone because sympathetic ␣-adrenergic-mediated vasoconstriction partly depends on L-type Ca 2ϩ channels (14,28) and because nifedipine depletes intracellular Ca 2ϩ stores in smooth muscle via inhibition of L-type Ca 2ϩ channels (15, 16,37) and possibly by a mechanism independent of L-type Ca 2ϩ channels in some types of arteries (10). Another finding of our study deserves some thoughts.…”

The Sarcoplasmic Reticulum, Ca2+Trapping, and Wave Mechanisms in Smooth Muscle

“…Two influx pathways, one voltage insensitive (i.e., not voltage gated) and one voltage sensitive (i.e., voltage gated), allow store refilling to be maintained over a wide membrane voltage range (12). Refilling appears to take place substantially from a subsarcolemma Ca 2+ pool in which Ca 2+ concentration exceeds bulk average cytoplasmic values.…”

“…Refilling appears to take place substantially from a subsarcolemma Ca 2+ pool in which Ca 2+ concentration exceeds bulk average cytoplasmic values. The Ca 2+ trap may contribute to the generation and maintenance of the high subsarcolemma Ca 2+ concentration to permit store refilling (12). In addition to the extracellular fluid source, the SR also plays an integral role in the generation of those Ca 2+ signals that give rise to the biological response.…”