HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Verheugen, J. A. H. Search for Related Content PubMed PubMed Citation Articles by Verheugen, J. A. H.

Elevation of intracellular Ca²⁺ in the physiologically relevant range does not inhibit voltage-gated K⁺ channels in human T lymphocytes

Jos A. H. Verheugen

1. Human T lymphocytes express both voltage-gated (K(V)) and Ca²⁺-activated (K(Ca)) potassium channels. The K(Ca) channel is activated by elevations of intracellular Ca²⁺ ([Ca²⁺]_i) at concentrations attained during physiological Ca²⁺ signalling. Whether or not the K(V) channel is affected by [Ca²⁺]_i is a matter of controversy. Here, the interaction between the K⁺ channels of lymphocytes and [Ca²⁺]_i was studied using cell-attached and whole-cell patch-clamp recordings, while [Ca²⁺]_i of the same cell was monitored simultaneously by fura-2 imaging or from the activity of the K(Ca) channels.

2. The K⁺ channels in cell-attached patches were measured using a high K⁺ pipette solution. The K(V) conductance was quantified as the integral of the inward current during voltage ramp stimulation, yielding a measure independent of the cell membrane potential. Whereas the open probability of the K(Ca) channel showed an absolute dependence on [Ca²⁺]_i, the K(V) channel was little affected by [Ca²⁺]_i. The K(V) conductance is not reduced by elevations of [Ca²⁺]_i in the range 0-8 µM. On the contrary, a modest but consistent increase in the K(V) current component in cell-attached currents was observed when [Ca²⁺]_i was elevated.

3. The absence of inhibition of the K(V) current by [Ca²⁺]_i was also apparent from whole-cell measurements with pipette solutions buffered to 1 µM free Ca²⁺: following break-in to whole-cell configuration, depolarizing voltage ramps were applied at regular intervals to activate the K(V) current while the K(Ca) current was measured from the slope of the ramp current below the activation of the voltage-gated current. During the gradual activation of the K(Ca) current, as the cell interior was perfused with the pipette solution, the K(V) current remained constant in amplitude.

4. In the initial period following break-in to whole-cell configuration, a gradual increase in the rate of K(V) current inactivation was generally observed. However, the time course of this change in kinetics was much slower than the perfusion of the cell interior, as judged from the activation of the K(Ca) conductance, ruling out a direct effect of Ca²⁺, within the physiological range, on K(V) channel kinetics.

This article has been cited by other articles:

				H. Rauer, M. Pennington, M. Cahalan, and K. G. Chandy Structural Conservation of the Pores of Calcium-activated and Voltage-gated Potassium Channels Determined by a Sea Anemone Toxin J. Biol. Chem., July 30, 1999; 274(31): 21885 - 21892. [Abstract] [Full Text] [PDF]

				C. M. Fanger, S. Ghanshani, N. J. Logsdon, H. Rauer, K. Kalman, J. Zhou, K. Beckingham, K. G. Chandy, M. D. Cahalan, and J. Aiyar Calmodulin Mediates Calcium-dependent Activation of the Intermediate Conductance Channel, IKCa1 J. Biol. Chem., February 26, 1999; 274(9): 5746 - 5754. [Abstract] [Full Text] [PDF]