Slow currents through single sodium channels of the adult rat heart.

Abstract

The currents through single Na' channels from the sarcolemma of ventricular cells dissociated from adult rat hearts were studied using the patch-clamp technique. All patches had several Na' channels ; most had 5-10, while some had up to 50 channels . At 10°C, the conductance of the channel was 9.8 pS . The mean current for sets of many identical pulses inactivated exponentially with a time constant of 1 .7 ± 0.6 ms at -40 mV . Careful examination of the mean currents revealed a small, slow component of inactivation at pulse potentials ranging from -60 to -30 mV . The time constant of the slow component was between 8 and 14 ms . The channels that caused the slow component had the same conductance and reversal potential as the fast Na' currents and were blocked by tetrodotoxin . The slow currents appear to have been caused by repeated openings of one or more channels . The holding potential influenced the frequency with which such channel reopening occurred . The slow component was prominent during pulses from a holding potential of -100 mV, while it was very small during pulses from -140 mV . Ultraslow currents through the Na' channel were observed occasionally in patches that had large numbers of channels . They consisted of bursts of 10 or more sequential openings of a single channel and lasted for up to 150 ms . We conclude that the single channel data cannot be explained by standard models, even those that have two inactivated states or two open states of the channel. Our results suggest that Na' channels can function in several different "modes," each with a different inactivation rate .

Stabilization of sodium channel states by deltamethrin in mouse neuroblastoma cells.

“…However, two conducting states for sodium channels have been reported in neuroblastoma cells (Nagy, Kiss & Hof, 1983 Patlak & Ortiz (1985) in sodium channels of adult rat heart. A lower rate of transition between the closed and open state would explain the increase in the time to the peak of activity in the averaged trace of modified single-channel current.…”

An investigation on the inactivation process of sodium currents in single frog ventricular cells.

“…There have been a number of reports using the voltage clamp method which indicate that the general properties of the cardiac Na + channel are similar to those in nerve cells (BRowN et al, 1981a, b;BODEwEI et al, 1982;BUSTAMANTE and MCDONALD, 1983;CACHELIN et al, 1983;MATSUKI and HERMSMEYER, 1983;BENNDORF et al, 1985;KUNZE et al, 1985;PATLAK and ORTIz, 1985). However, observations by some investigators of subtle differences in the time course of 1.…”

Endogenous polyamines regulate cortical neuronal excitability by blocking voltage-gated Na + channels

“…Moreover, when late channel activity was recorded in non-depleted slices, it took the form of sporadic, brief, late events. By contrast, the sustained bursts of openings, which are commonly attributed to transient entrance of the channel into a ''persistent'' or ''non-inactivating'' gating mode (11,14), were only observed in PA-depleted slices. In the latter, Na ϩ channels generated brief bursts of openings during most depolarizing pulses, and prolonged (Ͼ50 ms) bursts were observed in 3.3 Ϯ 0.6% of depolarizations ( Fig.…”

“…In single channel recordings, this ''modal gating'' is evident as prominent late openings during depolarizing steps (11). It is noteworthy that most experiments on Na ϩ current properties in central neurons have been performed under conditions which might limit the exposure of channels to endogenous cytoplasmic factors.…”