Deleting the accessory subunit KChIP2 results in loss of Ito,f and increased IK,slow that maintains normal action potential configuration

Rest potentiation, believed to be due to increased utilization of sarcoplasmic reticular calcium, was converted to rest depression by BAY K 8644 (1 microM). Plateau height and duration of the postrest beat were enhanced by BAY K 8644, suggesting an enhancement of extracellular calcium entry. Caffeine (3 mM) also produced depression at all rest intervals, although to a lesser extent than BAY K 8644. Compared with BAY K 8644, treatment with caffeine resulted in an elevation of plateau amplitude and a shortening of action potential duration. Action potential configuration changes induced by rest were unaltered by caffeine despite reduction in rest potentiation. Caffeine-induced rest depression was associated with an increase in the time to peak tension. This was not observed with BAY K 8644. Treatment with both caffeine (3 mM) and BAY K 8644 (1 microM) greatly prolonged time to peak tension. Action potential duration and plateau height were either maintained or increased. Less rest depression was observed with the combination than with either agent alone. These results suggest that 1) BAY K 8644 and caffeine inhibit rest potentiation by different mechanisms, and 2) caffeine-induced inhibition of calcium uptake by the sarcoplasmic reticulum may enhance the effect of BAY K 8644-induced increase in calcium influx on the contractile apparatus.

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Acetate-induced depression of electrical and contractile activity in normoxic and hypoxic guinea pig papillary muscle

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y89-118 ◽

1989 ◽

Vol 67 (7) ◽

pp. 734-739

Author(s):

Hideharu Hayashi ◽

Hajime Terada ◽

Alexander Kholopov ◽

Terence F. McDonald

Keyword(s):

Guinea Pig ◽

Action Potential ◽

Action Potential Duration ◽

Contractile Activity ◽

High Energy ◽

Factors Affecting ◽

Resting Tension ◽

Tension Increase ◽

Action Potential Shortening ◽

Action Potential Configuration

The action potential configuration, developed tension, and resting tension were monitored in normoxic and hypoxic guinea pig papillary muscles superfused with solutions containing no substrate, glucose, or acetate (1–10 mM). In normoxic muscle, acetate provoked a concentration-dependent transient depression of the action potential duration and force of contraction, depression was maximal after 10–30 min, and recovery was complete after 90–120 min. In hypoxic muscle, acetate accelerated functional rundown (action potential shortening, decline of developed tension, increase in resting tension). Because rundown in hypoxic muscle was sensitive to factors affecting glycolysis (moderated by external glucose; accentuated by 2-deoxyglucose), the accentuated rundown with acetate may be accounted for by a partial block of glycolysis. However, block of glycolysis cannot explain the acetate-induced transient depression in normoxic muscle, since the depression was enhanced in normoxic muscle with 2-deoxyglucose-blocked glycolysis. We suggest that the transient depression is due to a transient depression of high energy nucleotides with consequent effects on ionic currents.Key words: acetate, action potential duration, 2-deoxyglucose, hypoxia, ATP.

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