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

L. S. Satin, Steven Tavalin, P. D. Smolen

Research output: Contribution to journalArticle

21 Citations (Scopus)

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)

Original languageEnglish (US)
Pages (from-to)141-148
Number of pages8
JournalBiophysical Journal
Volume66
Issue number1
DOIs
StatePublished - Jan 1 1994

Fingerprint

Insulin-Secreting Cells
Action Potentials
Cadmium
Theoretical Models

All Science Journal Classification (ASJC) codes

  • Biophysics

Cite this

Inactivation of HIT cell Ca2+ current by a simulated burst of Ca2+ action potentials. / Satin, L. S.; Tavalin, Steven; Smolen, P. D.

In: Biophysical Journal, Vol. 66, No. 1, 01.01.1994, p. 141-148.

Research output: Contribution to journalArticle

@article{af2c884fa9284be88f1e1fbd9bdbd1f7,
title = "Inactivation of HIT cell Ca2+ current by a simulated burst of Ca2+ action potentials",
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)",
author = "Satin, {L. S.} and Steven Tavalin and Smolen, {P. D.}",
year = "1994",
month = "1",
day = "1",
doi = "10.1016/S0006-3495(94)80759-3",
language = "English (US)",
volume = "66",
pages = "141--148",
journal = "Biophysical Journal",
issn = "0006-3495",
publisher = "Biophysical Society",
number = "1",

}

TY - JOUR

T1 - Inactivation of HIT cell Ca2+ current by a simulated burst of Ca2+ action potentials

AU - Satin, L. S.

AU - Tavalin, Steven

AU - Smolen, P. D.

PY - 1994/1/1

Y1 - 1994/1/1

N2 - 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)

AB - 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)

UR - http://www.scopus.com/inward/record.url?scp=0027980128&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027980128&partnerID=8YFLogxK

U2 - 10.1016/S0006-3495(94)80759-3

DO - 10.1016/S0006-3495(94)80759-3

M3 - Article

VL - 66

SP - 141

EP - 148

JO - Biophysical Journal

JF - Biophysical Journal

SN - 0006-3495

IS - 1

ER -