Comparison of Na+ currents from type IIa and IIb human intercostal muscle fibers

Abstract

The voltage dependence and amplitude of Na+ currents (INa) were studied with the loose-patch voltage-clamp technique on 19 fast-twitch human intercostal skeletal muscle fibers at the endplate border and > 200 microns from the endplate (extrajunctional). The fibers were histochemically classified as fast-twitch oxidative-glycolytic (type IIa, n = 9) or fast-twitch glycolytic (type IIb, n = 10). The voltage dependence of activation and fast and slow inactivation of INa were similar for membrane patches recorded on the endplate border and on extrajunctional membrane for both fiber types. INa was about fivefold larger on the endplate border compared with extrajunctional membrane for both fiber types. Type IIb fibers had larger values of INa and manifest fast inactivation of INa at more negative potentials than type IIa fibers. The difference between type IIa and IIb fibers may enable IIb fibers to operate at higher firing frequencies for brief periods.

How myasthenia gravis alters the safety factor for neuromuscular transmission

“…We washed collagenase from the bathing chamber before recording currents. Additional details of the dissections are described elsewhere (Ruff, 1992; Ruff and Whittlesey, 1992; Ruff and Whittlesey, 1993a; Ruff and Whittlesey, 1993b). …”

“…To reduce capacitive coupling between the bath and pipette, we coated the pipettes with a double layer of Sylgard (Dow Corning 184, Midland, MI) to within 100 µm of the tip. We applied minimal suction to the micropipettes to avoid the formation of membrane blebs (Ruff and Whittlesey, 1993a). …”

“…were determined for rat and human muscle preparations, using previously described techniques (Ruff and Whittlesey, 1992; Ruff and Whittlesey, 1993a; Ruff and Whittlesey, 1993b). All intracellular microelectrode tips were coated with carbon black to mark an impaled fiber for later histochemical identification.…”

“…In addition to AChRs, the endplate membrane has a high density of voltage-gated Na + channels (Caldwell et al, 1986; Milton et al, 1992; Ruff, 1992; Ruff, 1996c; Ruff and Whittlesey, 1992; Ruff and Whittlesey, 1993a; Ruff and Whittlesey, 1993b; Wood and Slater, 1995). AChRs are concentrated on the crests of primary membrane folds channels, but voltage-gated Na + channels are concentrated in the depths of the secondary synaptic membrane folds (Angelides, 1986; Flucher and Daniels, 1989; Haimovich et al, 1987; Le Teut et al, 1990; Slater, 2007).…”

Defective slow inactivation of sodium channels contributes to familial periodic paralysis

“…[2][3][4][5][6]14 In contrast, in vitro studies on intact rat and human fast twitch skeletal muscle fibers found that slow inactivation developed at membrane potentials that were hyperpolarized compared with the operating ranges for fast inactivation. [8][9][10][11]15 Slow inactivation also developed at hyperpolarized potentials compared with fast inactivation for in vitro studies of frog twitch skeletal muscle fibers 12 and crayfish giant axons. 13 Consequently, in vitro studies of skeletal muscle and nerve suggest that slow inactivation may develop at hyperpolarized potentials compared with the voltage operating range shown in figure 3.…”