Protein kinase A modulates A-type potassium currents of larval zebrafish (Danio rerio) white muscle fibres
Potassium (K+) channels are involved in regulating cell excitability and action potential shape. To our knowledge, very little is known about the modulation of A-type K+ currents in skeletal muscle fibres. Therefore, we sought to determine whether K+ currents of zebrafish white skeletal muscle were modulated by protein kinase A (PKA). Methods:
Pharmacology and whole-cell patch clamp were used to examine A-type K+ currents and action potentials associated with zebrafish white skeletal muscle fibres. Results:
Activation of PKA by a combination of forskolin + 3-isobutyl-1-methylxanthine (Fsk + IBMX) decreased the peak current density by ∼60% and altered the inactivation kinetics of A-type K+ currents. The specific PKA inhibitor H-89 partially blocked the Fsk + IBMX-induced reduction in peak current density, but had no effect on the change in decay kinetics. Fsk + IBMX treatment did not shift the activation curve, but it significantly reduced the slope factor of activation. Activation of PKA by Fsk + IBMX resulted in a negative shift in the V50 of inactivation. H-89 prevented all Fsk + IBMX-induced changes in the steady-state properties of K+ currents. Application of Fsk + IBMX increased action potential amplitude, but had no significant effect on action potential threshold, half width or recovery rate, when fibres were depolarized with single pulses, paired pulses or with high-frequency stimuli. Conclusion:
PKA modulates the A-type K+ current in zebrafish skeletal muscle and affects action potential properties. Our results provide new insights into the role of A-type K+ channels in muscle physiology.