Modulation of the isoprenaline‐induced membrane hyperpolarization of mouse skeletal muscle cells

1 The hyperpolarization of the resting membrane potential, Vm, induced by isoprenaline in the lumbrical muscle fibres of the mouse, was investigated by use of intracellular microelectrodes. 2 In normal Krebs‐Henseleit solution (potassium concentration: K+o=5.7mM, ‘control’), Vm was −74.0 ± 0.2 mV; lowering K+o to 0.76 mM (′low K+o) resulted in either a hyperpolarization (Vm= −95.7 ±2.9 mV), or a depolarization (Vm= −52.0 ±0.3 mV). 3 Isoprenaline (≥200 nM) induced a hyperpolarization of Vm by ΔVm= − 5.6 ±0.4 mV in control solution. 4 When Vm hyperpolarized after switching to low K+o, the addition of isoprenaline resulted in increased hyperpolarization Vm: ΔVm=−16.3±3.2 mV to a final Vm=−110.1 ±3.4 mV. Adding iso‐prenaline when Vm depolarized in low K+o, leads to a hyperpolarization of either by − 11.6±0.5mV to −63.6 ±0.8 mV or by −51.7 ±2.7 mV to −106.9 ±3.9 mV. 5 Ouabain (0.1 to 1 mm) did not suppress the hyperpolarization by isoprenaline in 5.7 mM K+o (ΔVm=−6.7±0.4mV) or the hyperpolarization of the depolarized cells in low K+o (ΔVm=−9.7 Δ1.5mV). 6 The hyperpolarization is a logarithmically decreasing function of K+o in the range between 2 and 20 mM (12 mV/decade). 7 IBMX and 8Br‐cyclic AMP mimicked the response to isoprenaline whereas forskolin (FSK) induced in low K+o a hyperpolarization of −7.0 ±0.7 mV that could be augmented by addition of isoprenaline (ΔVm=−8.2±1.8mV). 8 In control and low K+o, Ba2+ (0.6 mm) inhibited the hyperpolarization induced by isoprenaline, IBMX or 8Br‐cyclic AMP. Other blockers of the potassium conductance such as TEA (5 mm) and apamin (0.4 μm) had no effect. 9 We conclude that in the lumbrical muscle of the mouse the isoprenaline‐induced hyperpolarization is primarily due to an increase in potassium permeability.