# MODES OF SINGLE NA CHANNEL GATING DURING LATE CURRENTS

> **NIH NIH R01** · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · 1990 · $130,782

## Abstract

The long-term objective of this continuing project is to characterize the
function of the Na+ channels in skeletal muscle and other tissues.  During
the next five years, effort will be dedicated to:

1.  Measure the rate and mechanism of kinetic change during bursting Na+
currents.  Previous work has led to the hypothesis that the kinetics of a
Na+ channel can occasionally change to new values, which are derived from a
broadly distributed range of possibilities for each rate.  The hypothesis
will be tested by measuring the distribution of opening and closing rate
constants in DPI 201-106 induced bursting behavior on mouse skeletal muscle
Na+ channels.  Further observations will determine the rate at which burst
kinetics can change for a single channel, the temperature dependence of this
process, and the mechanism of the change.

2.  Test whether fast-inactivating Na+ currents are due to homogeneous or to
changeable channels.  The null hypothesis that fast Na+ currents are due to
identical, unchanging channels will be tested by measuring the average
behavior of individual channels under conditions of low temperature.  The
mean current of each channel in a multi-channel patch will be determined by
subtracting currents before and after illumination with UV light, which
irreversibly destroys a portion (0, 1, or 2 channels) of the total channel
population.  Other statistical checks, such as "stability plots" of channel
open times, will also be used to try to test further this hypothesis.

3.  Measure alterations in Na+ channel subconductance frequency and
lifetime.  The molecular origins of sublevel events in channels are unknown.
Several new techniques now permit a quantitative measurement of the
amplitude and lifetime distributions of these events.  Experiments are
proposed to utilize these new techniques to measure the effects of
temperature, intracellular and extracellular pH, permeations, and patch
excision on the expression of subconductance levels.  The data will be used
to refine hypotheses for the mechanisms of these events.

4.  Examine the role of the cytoplasm in Na+ channel function.  Na+ channels
in mouse skeletal muscle are sensitive to alterations in their cytoplasmic
environment.  The rate and extent of "run-down" and the shift of the
inactivation curve will be used as assays of various artificial cytoplasmic
solutions.  The effects of pH, ionic conditions, temperature, osmotic
pressure, oxidation potential, and phosphorylation will be assayed for
direct effects on the alteration of channel properties upon patch excision.
If ineffective, crude extracts of muscle cytoplasm will be tested for their
activity.  Further isolation could identify such substances.

5.  Compare the properties of Na+ and Ca++ channels.  A number of functional
homologies exist between these two structurally homologous channels,
including mode-like gating behavior, steepness of voltage sensitivity,
subconductance level amplitude and lifetime.  These common functi...

## Key facts

- **NIH application ID:** 3158246
- **Project number:** 2R01AR037606-04
- **Recipient organization:** UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
- **SAM.gov UEI:** Z94KLERAG5V9
- **Principal Investigator:** JOSEPH B PATLAK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $130,782
- **Award type:** 2
- **Project period:** 1986-07-01 → 1994-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3158246

## Citation

> US National Institutes of Health, RePORTER application 3158246, MODES OF SINGLE NA CHANNEL GATING DURING LATE CURRENTS (2R01AR037606-04). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3158246. Licensed CC0.

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