Novel voltage-dependent non-selective cation conductance in murine colonic myocytes

Authors


Corresponding author S. D. Koh: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA. Email: skoh@physio.unr.edu

Abstract

  • Two components of voltage-gated, inward currents were observed from murine colonic myocytes. One component had properties of L-type Ca2+ currents and was inhibited by nicardipine (5 × 10−7m). A second component did not ‘run down’ during dialysis and was resistant to nicardipine (up to 10−6m). The nicardipine-insensitive current was activated by small depolarizations above the holding potential and reversed near 0 mV.

  • This low-voltage-activated current (ILVA) was resolved with step depolarizations positive to -60 mV, and the current rapidly inactivated upon sustained depolarization. The voltage of half-inactivation was -65 mV. Inactivation and activation time constants at -45 mV were 86 and 15 ms, respectively. The half-recovery time from inactivation was 98 ms at -45 mV. ILVA peaked at -40 mV and the current reversed at 0 mV.

  • I lva was inhibited by Ni2+ (IC50= 1.4 × 10−5m), mibefradil (10−6 to 10−5m), and extracellular Ba2+. Replacement of extracellular Na+ with N-methyl-d-glucamine inhibited ILVA and shifted the reversal potential to -7 mV. Increasing extracellular Ca2+ (5 × 10−3m) increased the amplitude of ILVA and shifted the reversal potential to +22 mV. ILVA was also blocked by extracellular Cs+ (10−4m) and Gd3+ (10−6m).

  • Warming increased the rates of activation and deactivation without affecting the amplitude of the peak current.

  • We conclude that the second component of voltage-dependent inward current in murine colonic myocytes is not a ‘T-type’ Ca2+ current but rather a novel, voltage-gated non-selective cation current. Activation of this current could be important in the recovery of membrane potential following inhibitory junction potentials in gastrointestinal smooth muscle or in mediating responses to agonists.

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