Biophysical Journal 66: 141-148 (1994)
© 1994 the Biophysical Society

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Inactivation of HIT cell Ca2+ current by a simulated burst of Ca2+ action potentials.

Department of Pharmacology and Toxicology, Medical College of Virgina, Richmond.

ABSTRACT

A novel voltage-clamp protocol was developed to test whether slow inactivation of Ca2+ current occurs during bursting in insulin-secreting cells. Single insulin-secreting HIT cells were patch-clamped and their Ca2+ currents were isolated pharmacologically. A computed beta-cell burst was used as a voltage-clamp command and the net Ca2+ current elicited was determined as a cadmium difference current. Ca2+ current rapidly activated during the computed plateau and spike depolarizations and then slowly decayed. Integration of this Ca2+ current yielded an estimate of total Ca influx. To further analyze Ca2+ current inactivation during a burst, repetitive test pulses to + 10 mV were added to the voltage command. Current elicited by these pulses was constant during the interburst, but then slowly and reversibly decreased during the depolarizing plateau. This inactivation was reduced by replacing external Ca2+ with Ba2+ as a charge carrier, and in some cells inactivation was slower in Ba2+. Experimental results were compared with the predictions of the Keizer-Smolen mathematical model of bursting, after subjecting model equations to identical voltage commands. In this model, bursting is driven by the slow, voltage-dependent inactivation of Ca current during the plateau active phase. The K-S model could account for the slope of the slow decay of spike-elicited Ca current, the waveform of individual Ca current spikes, and the suppression of test pulse-elicited Ca current during a burst command. However, the extent and rate of fast inactivation were underestimated by the model.(ABSTRACT TRUNCATED AT 250 WORDS)

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