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Activation of Ca(2+)-dependent K(+) channels contributes to rhythmic firing of action potentials in mouse pancreatic beta cells.

Göpel SO, Kanno T, Barg S, Eliasson L, Galvanovskis J, Renström E, Rorsman P - J. Gen. Physiol. (1999)

Bottom Line: The current was dependent on Ca(2+) influx but unaffected by apamin and charybdotoxin, two blockers of Ca(2+)-activated K(+) channels, and was insensitive to tolbutamide (a blocker of ATP-regulated K(+) channels) but partially (>60%) blocked by high (10-20 mM) concentrations of tetraethylammonium.This is similar to the interval between two successive bursts of action potentials.We propose that this Ca(2+)-activated K(+) current plays an important role in the generation of oscillatory electrical activity in the beta cell.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiological Sciences, Division of Molecular and Cellular Physiology, Lund University, SE-223 62 Lund, Sweden.

ABSTRACT
We have applied the perforated patch whole-cell technique to beta cells within intact pancreatic islets to identify the current underlying the glucose-induced rhythmic firing of action potentials. Trains of depolarizations (to simulate glucose-induced electrical activity) resulted in the gradual (time constant: 2.3 s) development of a small (<0.8 nS) K(+) conductance. The current was dependent on Ca(2+) influx but unaffected by apamin and charybdotoxin, two blockers of Ca(2+)-activated K(+) channels, and was insensitive to tolbutamide (a blocker of ATP-regulated K(+) channels) but partially (>60%) blocked by high (10-20 mM) concentrations of tetraethylammonium. Upon cessation of electrical stimulation, the current deactivated exponentially with a time constant of 6.5 s. This is similar to the interval between two successive bursts of action potentials. We propose that this Ca(2+)-activated K(+) current plays an important role in the generation of oscillatory electrical activity in the beta cell.

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Cell coupling does not account for Kslow current. (A) Membrane potential recording from a β cell in an intact islet. (B) Voltage-clamp recording at a holding potential of −70 mV. Changes of the cell conductance (G) were determined from the current responses (top) elicited by application of ±10-mV voltage pulses (200-ms duration, 2 Hz frequency; bottom). (C) Cell conductance calculated from the ±10-mV voltage steps in B. Note that the cell conductance is stable and amounts to ≈1 nS. In B and C, the shaded area indicated the silent interval between two successive bursts. (D) Current responses (top) elicited by a train of depolarizations followed by a series of ±10-mV voltage pulses applied from a holding potential of −70 mV to monitor the cell conductance (bottom). (E) Cell conductance (G) calculated from the ±10-mV voltage pulses. Note that the conductance is greatest (2.1 nS) immediately after the train, but subsequently declines to the steady state value (1.3 nS). The same cell was used in A–E.
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Figure 3: Cell coupling does not account for Kslow current. (A) Membrane potential recording from a β cell in an intact islet. (B) Voltage-clamp recording at a holding potential of −70 mV. Changes of the cell conductance (G) were determined from the current responses (top) elicited by application of ±10-mV voltage pulses (200-ms duration, 2 Hz frequency; bottom). (C) Cell conductance calculated from the ±10-mV voltage steps in B. Note that the cell conductance is stable and amounts to ≈1 nS. In B and C, the shaded area indicated the silent interval between two successive bursts. (D) Current responses (top) elicited by a train of depolarizations followed by a series of ±10-mV voltage pulses applied from a holding potential of −70 mV to monitor the cell conductance (bottom). (E) Cell conductance (G) calculated from the ±10-mV voltage pulses. Note that the conductance is greatest (2.1 nS) immediately after the train, but subsequently declines to the steady state value (1.3 nS). The same cell was used in A–E.

Mentions: Fig. 3 shows recording of glucose-induced electrical activity in a β cell in an intact islet (A) and the variations of the holding current subsequently measured in the same cell under voltage-clamp conditions (B, top). It can be observed that the holding current oscillates in a way reminiscent of inverted bursts of action potentials. This is because the electrical activity in the neighboring cells spreads into the voltage-clamped cells via the gap junctions, giving rise to oscillations in the holding current (Mears et al. 1995). Voltage pulses (±10 mV, 200-ms long, 2 Hz) were applied to monitor changes in the membrane conductance (B, bottom). The input conductance was the same during the silent intervals and the periods of action potential firing (Fig. 3 C, gray shaded area) and averaged 1.0 nS. When the same series of pulses were applied after a train of depolarizations, the membrane conductance (measured in the same β cell after lowering of the glucose concentration from 10 to 5 mM) was greatest at the end of the train and subsequently declined to a new steady state level (Fig. 3 D), from a starting value of >2.1 nS to a steady state value of ≈1.3 nS (Fig. 3 E). The latter value is higher than that measured in the presence of 10 mM glucose because the KATP conductance increased when the concentration of the sugar was lowered to 5 mM.


Activation of Ca(2+)-dependent K(+) channels contributes to rhythmic firing of action potentials in mouse pancreatic beta cells.

Göpel SO, Kanno T, Barg S, Eliasson L, Galvanovskis J, Renström E, Rorsman P - J. Gen. Physiol. (1999)

Cell coupling does not account for Kslow current. (A) Membrane potential recording from a β cell in an intact islet. (B) Voltage-clamp recording at a holding potential of −70 mV. Changes of the cell conductance (G) were determined from the current responses (top) elicited by application of ±10-mV voltage pulses (200-ms duration, 2 Hz frequency; bottom). (C) Cell conductance calculated from the ±10-mV voltage steps in B. Note that the cell conductance is stable and amounts to ≈1 nS. In B and C, the shaded area indicated the silent interval between two successive bursts. (D) Current responses (top) elicited by a train of depolarizations followed by a series of ±10-mV voltage pulses applied from a holding potential of −70 mV to monitor the cell conductance (bottom). (E) Cell conductance (G) calculated from the ±10-mV voltage pulses. Note that the conductance is greatest (2.1 nS) immediately after the train, but subsequently declines to the steady state value (1.3 nS). The same cell was used in A–E.
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Figure 3: Cell coupling does not account for Kslow current. (A) Membrane potential recording from a β cell in an intact islet. (B) Voltage-clamp recording at a holding potential of −70 mV. Changes of the cell conductance (G) were determined from the current responses (top) elicited by application of ±10-mV voltage pulses (200-ms duration, 2 Hz frequency; bottom). (C) Cell conductance calculated from the ±10-mV voltage steps in B. Note that the cell conductance is stable and amounts to ≈1 nS. In B and C, the shaded area indicated the silent interval between two successive bursts. (D) Current responses (top) elicited by a train of depolarizations followed by a series of ±10-mV voltage pulses applied from a holding potential of −70 mV to monitor the cell conductance (bottom). (E) Cell conductance (G) calculated from the ±10-mV voltage pulses. Note that the conductance is greatest (2.1 nS) immediately after the train, but subsequently declines to the steady state value (1.3 nS). The same cell was used in A–E.
Mentions: Fig. 3 shows recording of glucose-induced electrical activity in a β cell in an intact islet (A) and the variations of the holding current subsequently measured in the same cell under voltage-clamp conditions (B, top). It can be observed that the holding current oscillates in a way reminiscent of inverted bursts of action potentials. This is because the electrical activity in the neighboring cells spreads into the voltage-clamped cells via the gap junctions, giving rise to oscillations in the holding current (Mears et al. 1995). Voltage pulses (±10 mV, 200-ms long, 2 Hz) were applied to monitor changes in the membrane conductance (B, bottom). The input conductance was the same during the silent intervals and the periods of action potential firing (Fig. 3 C, gray shaded area) and averaged 1.0 nS. When the same series of pulses were applied after a train of depolarizations, the membrane conductance (measured in the same β cell after lowering of the glucose concentration from 10 to 5 mM) was greatest at the end of the train and subsequently declined to a new steady state level (Fig. 3 D), from a starting value of >2.1 nS to a steady state value of ≈1.3 nS (Fig. 3 E). The latter value is higher than that measured in the presence of 10 mM glucose because the KATP conductance increased when the concentration of the sugar was lowered to 5 mM.

Bottom Line: The current was dependent on Ca(2+) influx but unaffected by apamin and charybdotoxin, two blockers of Ca(2+)-activated K(+) channels, and was insensitive to tolbutamide (a blocker of ATP-regulated K(+) channels) but partially (>60%) blocked by high (10-20 mM) concentrations of tetraethylammonium.This is similar to the interval between two successive bursts of action potentials.We propose that this Ca(2+)-activated K(+) current plays an important role in the generation of oscillatory electrical activity in the beta cell.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiological Sciences, Division of Molecular and Cellular Physiology, Lund University, SE-223 62 Lund, Sweden.

ABSTRACT
We have applied the perforated patch whole-cell technique to beta cells within intact pancreatic islets to identify the current underlying the glucose-induced rhythmic firing of action potentials. Trains of depolarizations (to simulate glucose-induced electrical activity) resulted in the gradual (time constant: 2.3 s) development of a small (<0.8 nS) K(+) conductance. The current was dependent on Ca(2+) influx but unaffected by apamin and charybdotoxin, two blockers of Ca(2+)-activated K(+) channels, and was insensitive to tolbutamide (a blocker of ATP-regulated K(+) channels) but partially (>60%) blocked by high (10-20 mM) concentrations of tetraethylammonium. Upon cessation of electrical stimulation, the current deactivated exponentially with a time constant of 6.5 s. This is similar to the interval between two successive bursts of action potentials. We propose that this Ca(2+)-activated K(+) current plays an important role in the generation of oscillatory electrical activity in the beta cell.

Show MeSH
Related in: MedlinePlus