The contribution of voltage-gated Ca2+ currents to K+ channel activation during ovine adrenal chromaffin cell...

Prior to the development of adrenal innervation, the adrenal medulla is capable of responding to low blood oxygen directly. However, this response is lost once adrenal innervation is established. Previous work by our group has outlined mechanisms involved in this direct hypoxic response and the means by which innervation causes the loss of the direct hypoxic response in the ovine adrenal. The current study further investigates mechanisms which may underlie the developmental loss of the direct hypoxic response by concentrating on two aspects of cell function which regulate catecholamine secretion: the contribution of different types of Ca2+ channels to the total Ca2+ current and the contribution of each Ca2+ channel type to K+ channel activation. We identified that Ca2+ current size at -40 to -10 mV is increased in amplitude in fetal chromaffin cells. This is not due to the increased prevalence or size of T-type Ca2+ currents present at these voltages. The relative contribution of L-, N- or P/Q-type Ca2+ channels to total Ca2+ current and to activation of the K+ current is unchanged during chromaffin cell development, however K+ current density increases with age. Our results indicate that there is a developmental shift in relative expression of T-type, but not L-, N- or P/Q-type, Ca2+ channels in ovine chromaffin cells. The increased K+ current density in adult cells may result in an altered response to an equal stimulus, while larger Ca2+ current at negative voltages in fetal cells may facilitate Ca2+ entry and catecholamine secretion in response to small depolarisations such as those induced by hypoxia.